Spinning and Applications of Bioinspired Fiber Systems - ACS Nano

Subscriber access provided by WEBSTER UNIV

Review

Spinning and Applications of Bioinspired Fiber Systems Luoran Shang, Yunru Yu, Yuxiao Liu, Zhuoyue Chen, Tiantian Kong, and Yuanjin Zhao ACS Nano, Just Accepted Manuscript • Publication Date (Web): 15 Feb 2019 Downloaded from http://pubs.acs.org on February 15, 2019

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Spinning and Applications of Bioinspired Fiber Systems Luoran Shang 1,3, Yunru Yu 1, Yuxiao Liu 1, Zhuoyue Chen 2, Tiantian Kong*,2, Yuanjin Zhao*,1 1 State

Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering,

Southeast University, Nanjing 210096, China. 2

Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging,

Department of Biomedical Engineering, Shenzhen University, Shenzhen 518060, China. 3

School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts

02138, USA. Email: [email protected] (T.T. K.); [email protected] (Y.J.Z.)

ABSTRACT: Natural fiber systems provide inspirations for artificial fiber spinning and applications. Through a long process of trial and error, great progress has been made in recent years. The natural fiber itself, especially silks, and the formation mechanism are better understood, and some of the essential factors are implemented in artificial spinning methods, benefiting from advanced manufacturing technologies. Besides, fiber-based materials produced via bioinspired spinning methods find an increasingly wide range of biomedical, optoelectronics, and environmental engineering applications. This paper reviews recent developments in the spinning and application of bioinspired fiber systems, introduces natural fiber and spinning process, artificial spinning methods, and discusses applications of artificial fibers materials. Views on remaining challenges, and perspective on the future trends are also proposed.

ACS Paragon Plus Environment

1

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 84

KEYWORDS: silk; wet spinning; dry spinning; electrospinning; microfluidic spinning; direct writing; direct drawing; functional fibers

Fiber spinning is a highly specialized and efficient process. It exists in a variety of arthropod lineages and other species for hundreds of millions of years, among which the most wellunderstood examples are silk spinning in spiders and silkworms.1,2 Their specialized gland serves as a sophisticated spinning apparatus, through which protein dope can be continuously transformed into fibers. Natural silk fibers show extraordinary features, such as good mechanical properties and biocompatibility, and could be used directly in daily life.3-5 In addition to silks, many other biosynthesized fibers exhibit specific morphological (e.g. multi-compartmental, bead-on-string) or functional (e.g. fog collection) features. On one hand, these natural fibers provide inspirations for artificial fiber processing. On the other hand, the use of fiber-derived materials for specific purposes often calls for combinative properties that might be absent in natural fiber products. Therefore, bio-inspired artificial fiber systems have been put forward, with the aim of achieving fibers with on-demand performances as well as high output. To produce artificial fibers with features comparable to that of the natural products, efforts have been made to reveal the mysteries of biosynthesized fibers as well as the spinning processes. Specifically, natural silk spinning is a fiber pulling process by which a fluid dope could be forced through a spinneret and then converted into solid filaments continuously. The key to this process includes physicochemical parameters such as chemical composition, micro-nanostructure, ion concentration, as well as processing parameters such as the spinneret geometric feature, which shows strong impact on the shear forces involved.6-9 In recent decades, natural silk fibers and the spinning mechanisms are better understood through in-depth studies at the molecular and genomic


2

Page 3 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

levels, which provide considerable details and thus serve as an important inspiration in the optimized design of artificial spinning systems.10-12 In addition, benefited from the progress in materials manufacturing technologies, artificial fibers could be controllably generated by a variety of methods, including wet spinning, dry spinning, electrospinning, microfluidic spinning, direct drawing, and direct writing.13-15 These techniques facilitate spinning of not only silk protein fibers, but also a large variety of polymer materials with desired morphological and functional features that mimic other types of natural fiber. Besides, through appropriate modification and enhancement treatments, together with the incorporation of functional ingredients, the resultant fibers could be endowed with distinctive structural, optical, and electronic features. Taken together, the emerging spinning of functional fibers and fiber-based materials has given rise to a flourishing generation, contributing to increasingly wide range of applications such as tissue engineering, drug delivery, sensors and actuators, wettability manipulation, electrical generator, micromotors, to list a few.16-20 In this paper, we present an overview of recent developments in the spinning and application of bioinspired fiber systems. In section 2, we briefly introduce the natural spinning process and direct usage of natural fibers. Section 3 provides a detailed description of different artificial spinning techniques; their distinct strengths and limitations are discussed. Section 4 discusses functions and applications of artificial fibers and fiber-based composite materials. Section 5 gives a general summary, provides critical thinking about current limitations, and perspective on the future trends of artificial spinning approaches and fiber-based materials. NATURAL SILK FIBERS A large number of arthropod lineages possess spinning ability during different life stages and for different purposes.1 Besides, other species also produce high-performance fibers. For example,


3

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 84

mussel byssus is generated through a self-assembling process from protein precursors and shows exceptional properties including wet adhesion and self-healing;21 draw-processed hagfish slime threads exhibit comparable mechanical performance to the spider dragline silk;22 velvet worm generates stiff biopolymeric fibers through extruding an adhesive slime and subsequent drying and self-assembling.23 Natural fibers show excellent properties and thus offer inspirations for artificial fiber fabrication. Herein, we focus mainly on the most notable and well-understood examples, i.e., the domesticated silkworms (Bombyx mori) and spiders, both of which generate silks under ambient conditions. As shown in Figure 1A(i) and Figure 1B(i), B. mori generates silks for cocoon formation when it undergoes metamorphosis from larva to moth.4 By contrast, spiders produce silks for multiple purposes. In some of the species (not all), it could be differentiated into seven different categories according to particular gland where it comes from. Major ampullate silk accounts for web-building or dragline, minor ampullate silk serves as a temporary scaffolding, pyriform silk helps to form attachment to substrate, flagelliform silk is used in the capture spiral, aggregate silk is responsible for adhesive functions, aciniform silk can be used for wrapping prey, and tubuliform silk is the outer silk of the egg sac. Among these, the most studied is dragline silk for its extraordinary mechanical features.5 In recent years, there are a large number of studies directed on the spider dragline and B. mori silk systems. On one hand, much similarities have been clarified regarding fiber protein architecture and fiber formation mechanism. Several factors including the pH gradients, shear forces, ion concentrations, and the dehydration process are confirmed to be crucial for protein’s secondary structure formation and transformation, as well as the final fiber yielding in both of the spinning systems. On the other hand, detailed investigations reveal that there are lots of difference concerning amino acid sequence, the protein primary structure as well as internal molecular process, which might contribute to the difference in the


4

Page 5 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

mechanical properties of the final product. The similarities and differences between these two model systems are summarized in Table 1. In the following part of this section, we introduce the mysterious natural spinning systems, identify the determining factors related to this process, and explore the performance and usages of the natural silk materials. Table 1. Comparative overview of the spider silk and B. mori silk systems Silk system spider silk

Purpose

dragline basic construct of low the web and safety line

B. mori silk

Gland

Protein component

major ampullate gland spidroin (tail, sac, funnel, and duct)

cocoon formation abundant

Silk system

spider silk

Production

B. mori silk gland (PSG, fibroin MSG, and ASG)

Amino acid sequence

Protein structural transition

Fiber formation mechanism and governing factors

dragline similar architecture of long acidification-triggered pH-shift, ion exchange, repetitive glycine and alanine-rich spidroin structure change dehydration, and shear forces sequences flanked by non- (β-sheet conversion); repetitive N and C termini. through intermolecular interactions

B. mori silk

different in amino acid sequences acidification-triggered and primary structure fibroin structure change (β-sheet conversion); via bimolecular events Tensile mechanical properties

Silk system Strength

Extensibility

GPa

Toughness

Initial Young’s modulus

MJ m-3

GPa

A. diadematus 1.1 major ampullate silk

0.27

160

10

B. mori cocoon 0.6 silk

0.18

70

7


5

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 84

Natural silk spinning process. Natural silk spinning is generally conducted in a specific spinning organ, or gland. The most widely studied are B. mori silk gland and the major ampullate gland which produces the dragline spider silk. Despite their different origins, there still remains similarities regarding the functions and spinning mechanisms. Specifically, both of the two glands could be divided into several parts,11,24 as depicted in Figure 1A(ii) and Figure 1B(ii). Each part of the gland contains different cell types and plays specific role. In prior to spinning, silk protein (fibroin for silkworm silks and spidroin for spider silks, respectively) is synthesized and stored stably at high concentration (fibroin concentration is typical larger than 25wt%,25 and spidroin is soluable even at 30-50wt%, in absence of chaotropic agents26), which is also called the “spinning dope”. Then, the protein solution is transported and exposed to elongational flow, where it’s conformation changes in response to environmental variations including mechanical and chemical factors, as discussed in detail below. Afterwards, the silk protein undergoes a series of physical and chemical processes including phase separation and self-assembly, and ultimately aggregates into a solid, insoluble fibrous state. Finally, the fiber detaches from the gland walls and is pulled out by the movement of the silkworm’s larval head or the spider’s leg. Recent advances in genetics, molecular biology, physiology and biochemistry foster the detailed understanding of natural spinning process, including in the protein sequences, their crystal structure, and the regulatory factors that govern the formation of silks. Silk proteins are typically large molecules, with specific repetitive motifs and nonrepetitive domains. These features are relevant to the molecular events and secondary structure transformation, and also affect the mechanical features of the final fibers.12, 14 It has been confirmed that natural silk protein contains long repetitive domain flanked by shorter nonrepetitive amino and carboxy-termini.3 Despite the


6

Page 7 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

differences in sequence and primary structure of the B. mori and dragline spider silk systems, there are many similarities regarding the overall protein architecture. However, only by studying the molecular constituents is not enough to fully explain why silk fibers are generated with the unparallelled properties, and two key points concerning the intricate spinning process should be interpreted. One is the organization of the protein dope when stored before spinning, and the other is the controlled protein structure transformation, which, along with other complex processes, eventually contributes to solid fiber generation. There are different models being proposed about the amino acid motifs and the formation of high-order structures of the fiber proteins (which account for stable storage of the spinning dope in high concentration without using organic solvent or chaotropic agent), as well as the protein-to-fiber transformation and assembling mechanisms.10,27,28 One is a micellar structure where the hydrophilic terminal domains form a shell and the hydrophobic blocks are shielded internally. Another one is a liquid crystalline structure that allows for silk protein’s flow behavior while at the same time maintains some orientational order of molecular alignment. A latest work by Holland et al. revised the current micelle model for the storage and initial transformation ofspidroins. By combining the solution phase diffusion NMR and cryogenic TEM, they revealed directly that the spidroins initially exist as more complex, hierarchical assemblies composed of micelle subdomains in networks. These subdomains then undergo structural transformation of fibrillization upon shear, before liquid crystalline organization happens during silk spinning.28 The final solid fiber contains β-sheet crystals (converted from the alanine-rich repetitive domain) connected by amorphous regions (the alaninerich repetitive domain glycine-rich repeats). Several environmental parameters have been identified crucial for the phase transition of the proteins from high-density liquid to a solid state. Taking spider silk as an example, by using sensitive dyes or ion selective microelectrodes, pH


7

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 8 of 84

value has been measured in different regions of the glands, revealing a well-controlled gradient decrease along the transport path of the protein dope.11 The acidification of the dope, in combination with a CO2 concentration rise leads to secondary structure transition. The generation and maintenance of pH gradient is highly relevant to the presence of carbonic anhydrase (CA) enzymes produced by specific cells, and the responsive change of protein conformation is attributed to certain pH-sensitive terminal domains. In addition to pH variations, the concentration changes of ions such as Na+ and K+ also play a role in the fiber’s formation pathway.29 Apart from these chemical factors, mechanical effects have been demonstrated vital to the fiber formation and influence the tensile properties of the final fibers. Upon spinning, the protein dope flows through a region of contracting geometry and is subjected to shear and elongational flow that stretch the molecules.30 This leads to rheological change of the non-Newtonian protein fluid, transition of its molecule’s orientation and conformation, and flow-induced protein crystallization. To characterize the influence of stretching on the fiber’s mechanic features, forced silking has been conducted. Instead of spinning naturally, the spider or silkworm silk is controllably reeled using a rotating mandrel.31-33 As demonstrated by Vollrath et al., the increase of reeling speed would result in decrease of silk breaking strain and increase of breaking stress and initial modulus.32 Conventional use and advanced modification of natural silk fibers. The highly optimized spinning system let natural silk fibers stand out with spectacular and distinctive properties, and thus have been taken for direct use by mankind for a very long history. For example, silkworm has been domesticated for thousands of years beginning in ancient China.34 Due to its esthetic and lustrous appearance, soft texture, good mechanical properties, moisture ability, and the ease of farm, silkworm silk has been most notably applied in textiles industry and world commerce since ancient times. One of the most dramatic archeological discoveries of ancient silk fabrics is the


8

Page 9 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

“Gauze Gown in Plain Colour”, which was unearthed in Mawangdui Han Tombs in Changsha, China.35 It has of an area around 2.6 m2 and weighs only 49g, thus well-known as “thin as a cicada wing” and “light as smoke”. It represents the highest level of silk textiles technology of the early Han Dynasty, which dates to over 2000 years ago. Even till today, silkworm silk has remained to be an important resource to produce luxury apparel and furnishings. Spider silk generally shows extraordinarily high tensile strength, the maximum of which even exceeds that of the steel.5 Meanwhile, it also exhibits good extensibility. Such astonishing combination of strength and extensibility endows the fibers with high toughness. This, along with biocompatibility and biodegradability, makes it incomparable by most synthetic fiber materials. For this reason, spider silks have been employed as wound dressings in military service by ancient Greeks, and as fishing supplies by people in South Pacific areas. New Guinea residents use a wooden frame to entice the spiders into weaving nets with desired shape and size.36 Also, people in the Solomon Islands make a special spiderweb lure to catch fish in an innovative way called kite fishing, where the lure is dangled below a kite and thus could fly and bounce along the water surface.37 Apart from conventional utilizations, a research boom has emerged and continues in recent decades about modification of natural silks as well as the construction of silk-based composite materials, with the aim of further exploiting their potential in both construction industry and fundamental studies. Silk modification could be achieved by chemical and physical methods. The diverse chemical groups in silk proteins allow for site-specific modifications of the amino acid residues, thereby introducing functional characters or improving the existing features. In addition to chemical methods, the properties of silks have been found relevant to physical factors. For instance, Vollrath et al. found that the mechanical features of silkworm silks could be adjusted by controlling the harvesting and washing process. By artificially reeling the fibers straight from the


9

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 84

silkworms, the resultant fibers showed superior strength and extensibility than the naturally generated counterparts. The results thus suggested that silkworm silks might achieve comparable strength with that of the spider silks by tuning the spinning habits, rather than through gene alternation.38 Besides, silk-based composites could be derived by directly incorporating other ingredients, therefore combining the functions of both components. For example, Knez et al. infiltrated different kinds of metals into spider dragline silks through multiple pulsed vapor-phase infiltration (MPI) process.39 As shown in Figure 2A, after such treatment, the original recoverable hydrogen bonds were broken, allowing for metal ions’ infiltration and binding to form permanent metal-coordinated or covalent bonds. Thus, the fibers toughness was enhanced, which was highly favorable for biomedical applications. Despite these successful attempts, it should be noted that the enhancement of one property, either by physical or chemical modifications, might work at the expense of other properties. Therefore, overall consideration is needed in searching for an optimum solution. While the above-mentioned techniques focus on post-treatment or direct inclusion after fibers generation, recent years have also seen a trend of using intrinsic, biological strategies through genetic modification or diet alternation. Specifically, genetic engineering technique has been employed to insert the specific functional gene in the silkworm genome and then co-express it with the fibroin protein during the spinning process. For example, Jarvis et al. presented transgenic silkworm lines that could spin composite fibers integrated with spider silk protein sequences.40 The resultant fibers showed increased toughness, which was higher than the original silkworm silks, and was even comparable to the dragline spider silks. In contrast to gene alternation, another approach has been adopted by feeding silkworms with a special diet that contains dyes, functional molecules (drugs, nutrients, and stimuli-responsive compounds), or even nanomaterials. Han et al.


10

Page 11 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

fed the silkworms with a series of fluorescent dyes for in vivo uptake. In this way, a series of intrinsically multicolored and luminescent silks were directly produced, as shown in Figure 2B.41 Compared with external dying of the silks, this method was more convenient and environmentallyfriendly because it eliminated additional steps such as removal of excess chemicals, and avoided alternations of fiber properties that would be caused by harsh conditions.42 The similar method has been employed by many researchers, and composite silks have been spun with a colored or luminescent feature, enhanced mechanic properties (by feeding silkworms with single-walled carbon nanotubes or graphene43), or with functional loads. Such materials are highly expected to expand the application potentials of silk composites in biomedical imaging and sensing, drug delivery, and therapeutics.4,44-46 Beyond its original fibrous form, silk also shows versatile processability, and the natural silk proteins serve as important polymer sources to be reconstructed into other morphologies, including but not restricted to sponges, films, gels, particles, and other complex forms, as shown in Figure 2C. To this end, the raw silks are first collected and dissolved into solvents. Then, the proteins could be tailored into different formats by different processing strategies. For example, sponges could be obtained through freeze-drying or by using porogens;47 hydrogels are typically derived via sol-gel transition under certain trigger conditions such as heat treatment, mechanical force, ionic change, and UV irradiation;48,49 films could be fabricated by spin-coating or casting methods;50,51 particles and capsules could be prepared by emulsion/particles templated process.52,53 Also, silk-derived materials with special patterns could be fabricated through a molding method.54 The properties of the final products could be adjusted by many factors including the initial protein concentration and the environmental parameters involved in the specific treatment. In addition, by incorporating functional ingredients e.g., biomolecules, nanoparticles, silk composites could be


11

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 Spinning 48 49process 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 84

fabricated to generate functionalities including cellular response, sensing ability, and specific optical/electrical properties, while preserving its intrinsic advantages. These regenerated silk materials have found vast applications not only in biomedical fields including tissue engineering, drug delivery, and implantable materials, but also in a broad range of electronic and photonic devices such as supercapacitors, optoelectronics, and energy harvesters. Readers interested in this area are directed to excellent reviews for more details.4,55-57 ARTIFICIAL SPINNING METHODS The burgeoning application values of fiber-based materials in both commercial and research areas have triggered an increasing demand for their high quality and quantity. Natural spinning fibers possess outstanding properties and strongly promote the development of bioinspired spinning methods for mass-production of artificial silk fibers. In addition, the use of other kinds of fiber-derived materials for specific purposes often calls for a combinative property that might be absent in natural fiber products. Therefore, advanced artificial spinning has been proposed, with the aim of generating fibers with high production, well-controlled features, and made-to-order performance. In this section, we classify artificial spinning approaches, focus on the technical points, and summarize the processing-determining parameters for each method, respectively (Table 2). We also explore the diversity of fiber materials derived from these techniques, including artificial silks and other fibers. Table 2. Summary of natural and artificial spinning methods. Determining parameters

Production rate

Fiber diameter

Fiber morphology

Advantage

Typical Applications


12

Page 13 of 84 1 2 3 Natural 4 spinning 5 6 7 8 9 10 11 12 13 14 15 Dry 16 17 spinning 18 19 20 21 22 23 Wet 24 25 spinning 26 27 28 Electro29 30 spinning 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

textiles;35

yielding natural fibers with extraordinary mechanical features

fishing supplies;37

2.5-4 μm

solvent content; on the order dope of 101 m/s concentration; PH; temperature; post processing

several single fiber microns to hundreds of microns

fast and sensor;73 efficient, mild biomaterials;75 condition;

solvent/coagulant on the order content; of 100 m/s temperature; post processing

tens of single fiber microns to over one millimeter

fast and optomechnical device;128 efficient, wide 202 commercial use supercapacitors

(spider silk);

5-10μm

weaving web, wrapped egg sac (spider);

mild condition;

spinneret on the order geometry; PH of 10-2 m/s gradient; CO2 and ions concentration; shear force; reeling speed (forcibly)

non-woven cocoon (silkworm)

wound dressing5

(silkworm silk)

solution on the order microns to properties of 101 m/s submicrons (concentration, /nanometers volatility, surface tension, conductivity); equipment properties (electric field, nozzle configuration, nozzle-collector distance)

single fiber with porous, solid, coreshell, hollow and hybrid structures; non-woven mats

198 free from harsh micromotor solvent

generating submicronnanometer fibers; formation of mats

sensor;171 actuator;77 cell culture;81 cell 134-137 behavior regulation; tissue engineering;138,140,141,144148

wound dressing;143 controlled trapping/ release/delivery;153,155160,162,163

antibacterial matrix;149 fog collection;87 oil/water separation;187,188 liquid control;182


13

spreading

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Microfluidic 23 spinning 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 Direct 42 43 drawing 44 45 46 47 48 49 50 51 Direct 52 53 writing 54 55 56 57 58 59 60

Page 14 of 84

electric generator;194 conducting electrode203

core/sheath fluids on the order content; flow of 10-2 m/s rate; viscosity; channel configuration

hundreds of nanometers to hundreds of microns

single-fiber with solid, core-shell, hollow,

feasible for hydrogel materials; extremely flexible control multiover fiber compartmental, geometry and helix, and components patterning structures

sensor;101,173 cell culture,95,112 encapsulation;107,111,113 cell behavior regulation;93,98,109 tissue engineering;99,110,114,151,201 water collection;110,112,177179

controlled trapping/ 164 release/delivery; micromotor199 solution content on the order tens to single fiber and rheological of 10-1 m/s hundreds of properties; microns drawing rate

environmentally humidity absorption;118 friendly; tissue engineering;119 feasible for 120 multicomponent optoelectronic device; fibers sensor;170 generation fiber probe174

ink content and on the order several single fiebr; feasible rheological of 10-3 m/s microns to layer-by-layer hydrogel properties; hundreds of sequence; materials; microns

for tissue engineering;123,124


14

Page 15 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

nozzle coagulant

size;

patterned matrix

construction of micropatterened architectures

Wet spinning. Wet spinning refers to extrusion of the spinning dope solution into a bath containing certain coagulant agent. This method has been used in biomimetic fiber generation for decades. As illustrated in Figure 3A, the dope is pre-dissolved in a solvent solution, and then extruded into a non-solvent in the bath. The removal of the solvent leads to the precipitation of the dope into solid fibers. The key to this process is the chemical compositions of the reagents used, which directly affect the properties of the resultant fibers. First, the choices of proper solvent and the corresponding coagulant are very important, as there are several important factors that should be considered, such as the solvent/coagulant diffusion rate and temperature. Take biomimetic silk fibroin spinning as example, organic-based solvents have been reported in previously studies, such as hexafluoroacetone (HFA), 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), trifluoroacetic acid (TFA), N-methyl morpholine N-oxide (NMMO), and formic acid.13,58 In these systems, alcohols, especially methanol, ethanol, and isopropanol, are mostly selected as the appropriate coagulant agent. It is worth noting that, the coagulation conditions, including the coagulate type, content, and temperature, have an influence on the cross-section morphologies of the final fiber products because of differences in solvent diffusion and mass transfer.59 However, the toxicity of methanol restricted its industrial usage. Moreover, the rapid silk coagulation in methanol or ethanol and thus quick structural transformation of the silk protein would cause inadequate molecular chain orientation, which makes the fiber brittle.60 By contrast, aqueous ionic solvents such as LiBr have been explored, where salts solutions, e.g. ammonium sulfate could be coupled as the coagulant agent.60-63 Recent understanding of the high-concentration natural dope and pH-mediated


15

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 16 of 84

structural conversion has taken the aqueous-based spinning method a step further. A team led by Rising and Johansson reported a recombinant method, by which hybrid spidroin was obtained that combined the most soluble protein parts derived from two different spider species.64 By doing this, the aqueous solubility of the recombinant dope greatly increased compared to previously reported researches. Then, fibers were generated continuously by spinning into an optimized aqueous acidic buffer to induce pH drop, as shown in Figure 4A. Note that the natural silk spinning involves a stress-induced conformational change, where the alanine-rich domains form β-sheet to crosslink the protein molecules, and the protein molecules could align and crystallize in parallel to the fiber axis, which contributes to the tensile strength. In order to assess the degree of biomimicry, Jaudzems et al. used NMR spectroscopy to probe the domain-specific structural change of minispidroin (β-sheet formation and β-to-α change) in a wet-spinning process.65 In addition, this structural basis has been recapitulated in block copolymer fiber engineering. For example, Sogah et al. reported wet-spinning of oligoalanine-poly (ethylene glycol) multiblock copolymer fibers. The alanine oligomer segments served as β-strand forming peptides, and antiparallel β-sheet aggregates were experimentally confirmed in the resultant fibers. Increasing the peptide chain length led to a higher tendency of β-sheet motif formation, therefore improving the fiber modulus and tensile strength.66 Apart from tailoring the physicochemical parameters, the processing parameters are also important. To mimic the hydrodynamic flow and shearing, the spinning dope could be extruded by syringe pumps through a needle, or by using a high-pressured gas cylinder via a spinneret.58,67 Besides, a post-drawing processing is also crucial for the enhancement of fibers’ mechanical properties by enhancing the molecule alignment order.68,69 A study done by Park et al. confirmed that the crystalline orientation of silk fibroin filament increases with the drawing ratio, and thus


16

Page 17 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

enhances the tenacity, whereas the crystallinity is not significantly affected.70 Lewis et al. concluded that the synthetic spider silk is brittle until being post-stretched, and its tensile strength increases with the stretch ratio, at the expense of strain.71 Heidebrecht et al. investigated the combined effects of varying molecular weight, additional terminal domains, and post-stretching on the mechanical feature, and achieved recombinant A. diadematus dragline silk with same or even higher toughness (189.0±33.4 MJ/m3) as its natural counterpart (167.0±65.3 MJ/m3).72 In general, longer-time coagulation, post drawing with a higher ratio, and the additional steamannealing process would enhance the order of molecular orientation and cause alignment of the fibers from a densely entangled state, therefore enhancing the mechanical performance of the products. Overall, wet spinning is a quick and efficient method, and is easy for generation of reelable fibers for scalable fabrication. Dry spinning. Dry spinning is a process similar with wet spinning except that the solidification of fiber occurred not in a liquid environment, but in an air environment through evaporation of the volatile solvent or after a cooling process, as shown in Figure 3B. Compared to wet spinning, this technique has just recently been employed for bio-inspired fiber production. To some extent, it is more like the natural process in terms of directly extruding aqueous solution in the air at ambient temperature and low hydrostatic pressure. The key to this process is the preparation of the spinning solution. In previously reported researches, dope with different concentrations have been tried, and the pH value in the solvent has also been optimized.10 Recently, Kaplan and Buehler stepped forward with insight on the rheological feature of the spinning dope in determining the bulk feature of the fibers.73 Using improved dissolution conditions, they obtained a mixture of partially dissolved B. mori silk microfibril (instead of completely dissolving into fibroin molecules) in HFIP with increased concentration and viscosity, which served as the dope. The dope possessed a liquid-


17

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 18 of 84

crystal-like texture, which was analogous to that of the natural nematic silk proteins and was prealigned to allow flow under shear. In this manner, the dope could maintain its orientation order and transformed easily into solid fibers under mild conditions during the simple dry spinning process, as shown in Figure 4Bi-4Biii. The regenerated fibers inherited the hierarchical structure and thus mechanical properties of natural spider silks (Figure 4Biv). In addition to adjustment of the dope property, post-processing is also necessary in most of the dry spinning processes, in order to enhance the fiber property. By further dehydration and reimmersion in a certain agent (for example ethanol aqueous solution), conformation transition of the molecule continues, and the mechanical feature of the resultant fibers could be improved.74 Besides, by adding specific fillers (including the carbon nanotube, cellulose nanocrystals, and graphene oxide.) into the spinning dope solution, different interactions occur between the silk protein and the fillers.75 This would affect the crystallization process and the mechanical property of the fiber materials could be reinforced. Overall, the dry spinning process shows some similarities with wet spinning, as both of them involve extrusion of silk protein/solvent solution through a spinneret, and postprocessing is applied to enhance fibers performance. The mainly difference lies in the solidification procedure, where the former method relies on evaporation/cooling and the latter one uses a non-solvent as the coagulant. Electrospinning. Electrospinning is a process of continuously drawing fibers through electrostatic forces. It is a relatively old technique dating back to over a century ago when ultrafine fiber was observed to be drawn through a viscoelastic fluid under a strong electric field. The basic principle of electrospinning was depicted in Figure 3C. Spinning solution is first pumped out by a syringe pump or pressured gas into the tip of a needle or spinneret. It initially forms a hemisphere drop due to surface tension. When high-voltage power was supplied between the needle and the


18

Page 19 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

grounded collector, the liquid droplet is charged and elongated into a cone shape (which is called a “Taylor cone”) as the electrostatic force balances out the surface tension. Then, by further increasing the applied voltage beyond a certain point, a jet emits from the apex of the cone and accelerates toward the collector, which eventually concentrates into solid fibers after solvent evaporation. In recent years, electrospinning has been rediscovered and refined, mainly due to its ability to produce ultrafine fibers with diameters down to submicron or nanometers. In addition, the fibers could form mats or yarn in either randomly oriented or highly aligned state, by twisting, using a stationary or rotating collector, or through control of additional magnetic/electrostatic forces.76,77 Besides, controlling over the fiber properties (size, composition, structure, surface morphology, and porosity) is highly flexible through adjusting of multiple parameters, including solution properties (concentration, volatility, surface tension, and conductivity) and equipment conditions (including the strength of the electric field, nozzle configuration, and the nozzlecollector distance). These features are favorable for the potential applications of fibers including textiles as well as biomaterials.16 Therefore, electrospinning has developed into a universal and versatile method for synthesizing fibers from a huge variety of materials. Electrospinning has been employed for the fabrication of artificial silk fibers using aqueous or organic-based solvents (pure aqueous solution or mixture with polymers, formic acid, HFIP, and HFA).78 During this process, the most important parameter is the solution concentration, which dominants the continuous generation of fiber and affects its uniformity, morphology, and diameter. Generally, it requires relatively high viscosity of the spinning dope so that the jets would not break into droplets and form beads (which is another phenomenon named as “electrospraying”). This could be achieved by increasing the protein concentration or by adding polymers such as poly (ethylene oxide) (PEO).79 In addition, the diameter of the fibers increases with the solution


19

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 20 of 84

concentration and is also affected by many other parameters regarding the dope and equipment. Similar with wet or dry spinning, electrospinning of silk fibers also needs post stabilization processing. For example. Eby et al. employed high-temperature annealing to achieve B. mori and N. Clavipes spider silk fibers with comparable crystalline orientations to that of the natural silk fibers.80 Park et al. performed chemical treatment to the regenerated silk fibroin nanofibers using methanol, thus increasing the silk fibroin nonwovens stability due to enhanced crystallinity.81 What distinguishes electrospinning most from these conventional approaches is the high elongation rate and ratio during fiber formation, which results in the formation of artificial silks with diameters in a wide range (tens to thousands of nanometers), even including fibers much smaller than the natural silks. It thus providing a direct characterization of possibly existing subsilk structures such as oriented crystalline patterns.78 For example, by using the electrospinining method, Scheibel et al. illustrated the function of mesoscale building blocks of single-component recombinant spider silk filament and measured the (nano-) mechanical properties. Their results elucidated that higher humidity condition enhances fiber extensibility by increasing protein chain mobility, but it also hinders β-sheets formation as the hydrogen binding sites are occupied and therefore decreases the strength of the fiber. This study links the molecular interactions to the macroscopic mechanical properties of spider silk.82 Apart from silks, there are many other biological fibrils/filaments materials with complex topographical structures that contribute to distinct functions, such as hairs, muscles, tendons, and plant roots. These materials inspired a cutting-edge direction in constructing functional fiber materials by mimicking the natural structural features. Owing to its versatility in operation and flexibility in spinneret design, electrospinning has evolved into an efficient bioinspired technique in mimicking these natural one-dimensional (1D) materials. For example, the hollow fiber


20

Page 21 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

structure in polar bear furs provides ideal insulation and warm keeping to help survive in the arctic cold environment.83 Multichannel tubular structures can be found in many birds for weight reduction. In order to mimic these structures, coaxial electrospinning setup was designed combining multiple coaxial capillaries into one spinneret (Figure 4Ci).84 By co-electrospinning multiple fluids through such spinneret, a compound jet formed and eventually resulted in the generation of fibers with programmable multichannel structures, as shown in Figure 4Cii. The similar strategy has also been used to generate fibers with multiple components arranged side-byside, as a mimic of the self-crimping wool fibers with inter-adhering components of orthocortex and paracortex.85 In addition to fibers with homogeneous geometry along the axial direction, fibers with a shape gradient have been observed in many organisms and confirmed to promote directional liquid transport. The most famous example is the capture silks of Cribellate spider, which harvest water from humid air.86 The silk possesses a wet-rebuilt structure of periodic spindle-knots and joints. The heterogeneous shape along the fiber axis results in a curvature gradient, which generates a Laplace pressure difference that promotes tiny water droplets to move from joints toward the knots. To mimic this structure, a combination of electrospinning and electrospraying strategies was developed in a coaxial jetting process, as illustrated in Figure 4Di.87 By using two concentrically arranged needles as the spinneret, an inner fluid of higher viscosity was spun into fibers and an outer fluid with lower viscosity was simultaneously sprayed into beads, which were imprinted on the fibers to form a “beads-on-fiber” structure, as shown in Figure 4Dii. Another example of bio-inspired archetype is the cactus spine, which shows conical shape with hierarchical groove structure, and exhibits intriguing abilities of drought resistance and fog collection in a similar principle. By combining electrospinning process with a sacrificial template method, composite fibers were first aligned on the surface of a conical needle, and nano-grooves patterns


21

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 22 of 84

were created after imidization-induced decomposition of one component, therefore generating artificial cactus spine.88 Overall, electrospinning technique possesses two distinguishing features. One is the efficiency of generating polymer (including but not limited to silk protein) fibers in a wide range of diameters. The other is that the resultant fibers could be conveniently engineered into matrices. Therefore, it allows for biomedical applications, including generating matrices with adjustable sizes could promote cellular interactions, which is significant for their application in biomedical applications such as tissue engineering. In addition, there are other aspects of applications such as in wettability control and energy generator, which are summarized in Table 3, and detailed information see Chapter 4. Table 3. Electrospinning functional fiber materials. Material

Solvent

Morphology

Diameter

Application

Ref

PAN

DFM

uniform

700 nm

chemo-mechanical actuation

77

silk PEO

fibroin/ LiBr

uniform

< 800 nm

-

79 80

silk protein

HFIP

uniform

6.5-200 nm

-

silk fibroin

formic acid

nonwovens

30-120 nm

cell attachment 81 /spreading

Ti (OiPr)4 /

ethanol

multichannel tubular

2.3 μm

-

84

PNiPAAm, P(MMA-coBMA)

chloroform, DMF

side-by-side, bead-onstring

1-3 μm

-

85

PEG, PS

DMF, chloride

10 μm

environmental wetting response

87

PAA-PS

DMF

< 200 μm

fog collection

88

poly (vinyl pyrrolidone)

methylene bead-onstring hierarchical groove


22

Page 23 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

PCL

chloroform-methanol

nanofibrous scaffolds

200-300 nm

neural tissue 134 engineering

PLLA

chloroformdichloromethane

aligned

2.49 μm

astrocytes scaffolds

PDMS (templated from PS, PC, PVA, and PVDF) PCL/ collagen

chloroform, DCM, aligned acetone, water

300nm-2μm neural guidance

hexafluoroisopropanol AutoCAD patterns

200-500 nm

3D tissue formation 137

135

growth 136

PVA-MA/ CS- water MA

3D scaffolds

500 nm

articular repair

PLGA

dichloromethane

fibrous scaffolds

1.5-2 μm

hypertrophic scars 140 repairing

PLLA/gelatin

trifluoroethanol

fibrous scaffolds

1.6 μm

neuronal stem cells 141 differentiation

PCL/gelatin/Au HFIP NPs

nanofibrous mats

~150 nm

antibacterial wound 143 dressing

PCL (core), TFE (core), zein(shell) AcOH(shell)

core/shell nanofiber membrane

0.5-0.8 μm

guided tissue 144 regeneration

silk PEO

aligned fiber 1-3 μm mats

tissue regeneration

nanofibrous scaffolds

stem cells 146 osteogenic differentiation and

fibroin/ formic acid

PCL/PLA

DCM/DMF

0.2-1 μm

cartilage 138

cranial formation

145

bone

ECM/PCL

HFIP

fibrous scaffolds

1-2 μm

meniscus regeneration

147

nylon 6/silver

formic acid

nanofiber mats

50-150 nm

antibacterial

149

nanofiber mats

370-530 nm

human platelet 153 lysate release

silk PEO

fibroin/ lithium bromide


23

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 24 of 84

PLLA

DCM, HFIP and EtOH fibrous scaffolds

1-2 μm

controlled release

PLGA/PDO

HFIP

fibrous membrane

~1 μm

controlled antibiotics release

156

PLA/carbon nanotube

chloroform/DMF

porous

~2 μm

protein/DNA trapping

157

PCL

TFE

fibrous scaffolds

~1.4 μm

RNA delivery

158

PVA

water

nanofiber mats

~110 nm

vascular endothelial 159

Eudragit S100 ethanol/DMAc (copolymer)

core-shell

~2 μm

PH release

PVA-magnetic NPs

water

uniform

100-300 nm

magnetic triggered 161 release

PCL-Mn-PS

DCM

nonwoven fabrics

1-10 μm

light release

PVA-micelle (core),

water(core),

core-shell

~210 nm

cancer Therapy

163

gelatin-genipin (shell)

acetic water(shell)

acid/

drug 155

growth release

factor triggered 160

triggered 162

(outer), ~80 nm (inner)

silk fibroin

formic acid

nanofiber membranes

~350 nm

pressure sensors

171

PET-CHI

TFA-DCM

fibrous film

~1 μm

unidirectional droplet spreading

182

PS

THF

porous fibrous film

0.5~2.135 μm

oil adsorption

187

PMIAMWCNT

LiCl/DMAc

3D nonwoven 134 nm membrane

oil-water separation 188

silk fibroin

HFIP

nanofibernetwork

bio-triboelectric generator

100-200 nm

194


24

Page 25 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

PAN

DMF

nanowire meshes

1.8 μm

conducting electrode

203

Microfluidic spinning. Microfluidics is a technique that manipulates microscale fluids within miniaturized channels of designed configurations.89 Due to its capacity in precise and systematic control over individual fluids and their interfaces, microfluidics has emerged as a fascinating approach in the synthesis of functional materials, including continuous fiber generation.16,90-94 The basic principle of microfluidic spinning is illustrated in Figure 3D. A dope fluid and a sheath fluid flow into a microfluidic device via two concentric channels and are brought into contact at the junction. As the fluids dimension shrinks to microscale, the flows are laminar, and mixing between the two fluids is dominated by slow diffusion at the interface. Therefore, phase separation occurs and the two flows form a coaxial configuration, with the core fluid of spinning dope hydrodynamically focused in the channel by the sheath fluid. By solidifying the core flow in situ, fibers could be extruded out through an outlet channel. As the sheath flow acts as a lubricant, the core flow would not directly contact the channel wall, therefore ensuring continuous fiber production without clogging the channel. Microfluidic spinning mostly works in a mild environment.95 In respect to specific solidification methods, selection of core and sheath fluids is crucial for the successful generation of fibers. For example, hydrogel fibers (e.g. polyethylene glycol diacrylate,96 methacrylamide-modified gelatin,93 poly(ethylene glycol) dimethacrylate97) could be achieved by ultraviolet-induced polymerization, using a photopolymerizable monomer as the core flow, with an addition of photo-initiators. For ionic or chemical crosslinking, polymer precursor and crosslinker (e.g. alginate and calcium ions,95 chitosan and sodium tripolyphosphate98) are presented in the core and sheath flow, respectively. Also, for solvent exchange, a pair of solvent and non-solvent is placed separately before diffusion-based exchange


25

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 26 of 84

occurs, and fiber is thus achieved by precipitation.99 In each of the process, the concentration of reagents, the flow rate of the streams, and rheological parameters (such like viscosity) all have certain effects on the properties of the resultants fibers. In general, for the stability of the fiber generation, a well-centered device configuration is required.94 The content of crosslinker or initiator affects the action-diffusion behavior and thus determines whether a compact small piece of fiber would form.100 The flow rate ratio and the viscosity ratio have an impact on the flow dynamics. By adjusting these parameters, a variety of flow regimes and thus fiber structures could be generated, including straight, wavy, helical ones.101 Microfluidic spinning is one of the most fascinating methods in mimicking silk spinning because it operates in the spirit of the essential hydrodynamic principles found in natural spinning processes. Owing to the laminar flow configuration, the relatively slow diffusion of liquids across the interfaces helps to create a precisely controlled gradient of pH. Also, by increasing flow rates, the shear force could be generated along the channel. In addition, it facilitates the generation and manipulation of a single fiber. Besides, the whole process could be observed in a time-resolved manner by means of optical microscopy or X-ray scattering. Therefore, it offers an intuitive platform to decipher the molecular assembly and conformational transformation mechanisms involved in the silk formation process.102,103 For example, Bausch et al. investigated the assembly mechanism of two variants of spider silk proteins (eADF3 and eADF4) in a custom-made microfluidic device.103 As shown in Figure 5Ai-5Aii, the device was composed of different channel modules for laminar mixing, elongational flow, and analysis, respectively. It was found that eADF3 assembled into fibers at the existence of elongational flow, increase of phosphate concentration, and a certain extent of pH drop (Figure 5Aiii). By contrast, eADF4 formed spherical colloidal assemblies rather than fibers under all conditions, unless mixed with eADF3.


26

Page 27 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

This might be attributed to an insufficient attractive force between eADF4 aggregates. These results indicated that the rheological behavior of silk protein, along with flow parameters, is an essential parameter in the process of dragline silk assembly. Bearing these merits in hydrodynamic imitation, microfluidics has emerged as an efficient approach for spinning of silk fibers. Wong et al. pioneered by combining a microfluidic experimental setup with a modeling method to generate silkworm fibroin fibers. A core flow of regenerated silk fibroin solution was sheathed by two streams of poly(ethylene oxide) with low pH. The fibroin stream then solidified to form fibers due to PH-initiated sol-gel transition. A servomotor-controlled syringe pump was used to control fluid hydrodynamics and thus help to accurately predict and customize fiber diameter. A post-drawing process resulted in an increase in Young's modulus and failure strain to match that of the natural B. Mori silks.104 They also took advantage of computational fluid dynamic simulations on the effect of shear and ion gradients, through which they developed a modeling system to aid in the design of future devices.105 In contrast to the conventional core-sheath flow regime, Hedhammar et al. applied. Dual fluid phases of a spidroin solution and oil flowed in parallel to form a laminar regime. The amphiphilic spidroin accumulated at the interface to form fibers in a continuous and instantaneous way. By using this method, the PH-relay role of the N-terminal domain found in the spidroin protein was also implemented in this artificial process.106 Besides, Lee et al. fabricated free-standing and meterlong silk fibroin fibers by introducing a “protection layer”. Alginate was used to help form an aqueous-two-phase system (ATPS) between fibroin through phase separation. The ATPS mixture was then spun into fibers after rapid crosslinking, with fibroin particles being entrapped in the alginate hydrogel, which could withstand extensive post-stretching and help to shape the fiber outline. The pure-fibroin fiber was then achieved after degradation of alginate.107 Apart from silk


27

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 28 of 84

fibers, microfluidic spinning allows for the fabrication of high-performance fibers from a variety of materials. For example, Söderberg et al. reported a wood-inspired fabrication of cellulose fibers through a flow-assisted assembly of cellulose nanofibrils.108 The resultant fiber shows extraordinary mechanical properties exceeding known biopolymeric materials, due to the exellent unidirectional alignment of the building blocks. Scheibel et al. achieved acidic-triggered assembly of collagen microfibers, which exhibit tensile strength and Young ’ s modulus superior to even natural tendon.109 In addition to the flexibility in materials choice, another prominent advantage of microfluidic spinning lies in the ability to integrate multiple fluids and control over each one with regard to its opening/closure state and flow rate. This principle has been widely implemented in the control over fibers morphology. Readers who wish to explore this area in detail could refer to specific reviews.16,95,96 Generally, the most common shape of microfluidic fibers is a solid cylindrical shape, while fibers with more complex configuration have also been generated in mimic of natural fibrous materials. For example, Lee et al. reported a coded fabrication of fibers with spatially designed morphologies and compositions.110 Inspired by the anatomic structure of the spiders spinning apparatus, with multiple glands being controlled individually by a valve, they constructed a PDMS microfluidic chip with several inlets and a digital fluid controller, as shown in Figure 5Bi-5Biii. Each inlet channel was controlled independently by a computer-controlled pneumatic valve, therefore enabled coded generation of fibers containing different materials that were twisted into triple-helix morphology (Figure 5Biv). Zhao et al. carried out a series of work on bioinspired microfluidic spinning using capillary-based chips. Through dual control of hydrodynamic behavior and channel configuration design, microfibers with diverse compositional and topographical properties mimicking natural tissues structures have been fabricated.111 At a relatively low flow


28

Page 29 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

rate of the core fluid, laminar flow occurs, and the resultant fibers followed the same configuration as the injection flows. By using a multi-barrel capillary as the injection tube, microfibers with anisotropic multicompartmental structures were prepared, as shown in Figure 5C. By contrast, when core flow increased to some extent, spiral fibers formed due to unbalanced friction between the fibers and fluid. This phenomenon, along with the design of the injection capillary, enabled generation of helical fibers with complex morphologies, even include double-helix structures, as shown in Figure 5D.101 In addition, they combined spinning with emulsification in a single microfluidic device composed of a coaxially-aligned two-layer injection capillary. Through control over the shear force, the outer layer fluid broke into spindle-shaped droplets and was strung on the fibers formed by the inner layer fluid (Figure 5Ei).112 Thus, hetero-structured fibers with periodic spindle-knots and joints were generated, as shown in Figure 5Eii-5Eiii. Based on this strategy, Liang et al. generated necklace-like microfibers with knots in diverse configurations (including spindle, hemisphere, and petal) and hollow channels with various structures (including straight, Janus, and helical). The merits of the fiber structure and the perfusability of the channel resulted in the diffusion gradient in the knot, which is similar to the nutrient supply in liver acinus.113 Instead of forming a string of droplets hung on the fibers, Qin et al. encapsulated droplets within the fibers, which could be shrunk into biomimetic bamboo-like morphology through a dehydrating procedure, as shown in Figure 5F.114 Direct drawing. Self-assembly of natural silk proteins occurs under a mild environment without extensive energy input. Inspired of this, recombinant miniature spidroins assembly has been achieved at the air-liquid interface along a tube.115 Moreover, researches have been focused on the generation of fibers by self-assembly through a direct drawing process, as illustrated in Figure 3E. A filament could be readily drawn from a liquid reservoir (generally an aqueous environment) into


29

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 30 of 84

a uniform solid fiber, and the solution concentration, as well as the drawing rate, would affect the fiber dimensions, accordingly. For this method, the materials used usually enable a self-assembly process occurring at the air-water interface by different mechanisms such as molecular interactions116 or polyelectrolyte complexation (IPC).117-119 For example, Scherman et al. directly drawn fibers from a mixture of dynamic supramolecular polymer-colloidal hydrogels, which was facilitated by a host-guest cross-linking process between methyl viologen (MV)-functionalized polymer-grafted silica nanoparticles (P1, the guest), a semicrystalline polymer of hydroxyethyl cellulose derivative (H1, another guest), and the cucurbit[8]uril (CB[8]), as the host), (Figure 6Ai6Aiii).116 The presence of the colloidal silica NPs contributed to stronger and more ordered networks (Figure 6Aiv). The resultant fibers could achieve arbitrary length, with a uniform cylindrical shape and hierarchical nanoscale fibrils feature, as shown in Figure 6Av-6Avii. It exhibited even better tensile and damping properties than that of spider silk. In addition, Ikkala et al. took cues from natural wool fibers and generated bicomponent fibers with side-by-side structures through the IPC process between anionic cellulose nanofibrils and polycations.118 The two fluids with oppositely charged polyelectrolytes formed an interface rapidly when contact, and self-assembled into continuous fibers under mechanical drawing. The rheological properties were found to affect the spinnability of the solution. Note that there is another drawing strategy, not based on self-assembly, but by using tensile force to stretch a glass (thermal drawing),120 or plastic material (cold drawing)121 into desired morphology and diameter. It has been widely employed in industrial manufacturing. Direct writing. Direct writing is a kind of additive manufacturing technique, which translates computer-designed 3D models directly into physical objects in a bottom-up manner. As shown in Figure 3F, it generally involves a pattern generating device (a nozzle or laser optics) attached to


30

Page 31 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

a computer-controlled translation stage, which could move and deposit the “ink” into desired locations and construct complex architectures layer-by-layer.122 The principle of direct writing could be implemented to facilitate silk fiber spinning due to its feasibility and convenience of producing fiber scaffold, which could find widespread applications in textiles and biomedical fields (see next Chapter). For example, Kaplan and Lewis et al. used an aqueous solution of regenerated silk fibroin as the ink, which was directly deposited through a micronozzle into a reservoir of methanol coagulant, thus generating fibers by rapid crystallization.123 In this process, the ink rheological properties were optimized to facilitate flowing through a microsized nozzle yet maintaining filamentary feature upon being extruded, the fiber diameter is affected by the nozzle size, and the coagulant content was also optimized to maintain the fiber shape yet flexible for scaffold adhesion. By this way, a 3D micro-periodic array of silk fiber scaffold could be formed, as shown in Figure 6B. Based on the same strategy, they further combined a silk fibroin solution with a hydroxyapatite suspension as ink and prepared composite scaffolds with controlled pore architectures.124 In addition to this, direct writing could be realized in a melt electro mode, where the electrostatic force is applied to a polymer melt.125,126 Diameter of fibers generated by this method could be tailored in the range of submicron to hundreds of microns, by tunning the nozzle size and the flow rate. Compared with conventional, solution-based electrospinning, it is solventfree and thus favorable in terms of environmental and health concerns. Others. The existing spinning techniques could be refined or combined for certain purposes. For example, inspired by muscles-mediated motions, Peng et al. produced helical assembled fibers with hierarchical structures through an improved dry spinning approach.127 Specifically, macroscopic multi-walled carbon nanotube was first assembled into a primary helical fiber. Then, one end of the fiber was stabilized while the other end was rotated. Therefore, the fiber was twisted


31

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 32 of 84

to form the secondary structure, as shown in Figure 6C. Kotov et al. combined wet-spinning with a twisting process, and fabricated helical nacre-mimic composite fibers, which showed exceptional toughness and optical asymmetry for circularly polarized luminescence.128 Yin et al. reported a solution blowing spinning method by which a Poly(styrene-b-isobutylene-b-styrene) fiber could be sprayed onto a different substrate through a painting-using airbrush controlled by a gas flow regulator.129 Minko et al. put forward a “magnetospinning” strategy to produce fine nanofibers.130,131 By using a permanent magnet fixed on a rotating stage, a polymer solution containing magnetic nanoparticles was pushed through a needle tip, drawn close to the magnet, and then stretched into fibers during the rotation process. Fiber diameters could be controlled by the polymer concentration as well as the magnet rotation speed. Compared with traditional electrospinning process, the formation of fibers was mediated by magnetic forces and hydrodynamic features, without using high voltages, and the spinnability was independent of the dielectric properties of the solution. Overall, each spinning technique has a distinct processing mechanism and controlling parameters, and are thus suitable for specific materials and application purposes. APPLICATIONS OF FUNCTIONAL FIBERS PRODUCED BY ARTIFICIAL SPINNING Artificial scaffolds. Animal extracellular matrix (ECM) is a collection of extracellular molecules that are secreted by cells. It consists of assembled nanofibrous proteins (including collagens, elastin, fibronectin, and laminin) being embedded within proteoglycan gels. ECM provides not only structural support but also biochemical cues to instruct dynamic behavior of the surrounding cells.132 Although diverse in compositions and arrangements between specific tissues or organs, common functions of ECM are the same in these multicellular structures, involving cellular adhesion, communication, differentiation, and certain other activities. With the


32

Page 33 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

increasingly high demand of tissue repair and clinical transplantation, construction of artificial matrices, or scaffolds, that mimic natural ECM has been proposed, which aims at recapitulating native ECM rules in supporting the cell and manipulating cell behaviors, hence eventually fulfilling tissue engineering and regenerative medicine applications. For this purpose, artificial scaffolds material should be biocompatible to minimize possible inflammation or immune responses. Also, a porous macroscopic structure is needed to optimize cell-matrix interaction and nutrients/oxygen transportation. In addition, it is desired to be mechanically matching to the surrounding tissue. With these requirements in mind, nanofibers scaffolds represent a promising solution because it takes inspiration straight from natural fibrous networks within the ECM.133 Construction of fiber-based artificial scaffolds has been prominently implemented in electrospinning method, whose advantages embody in the following aspects. First, it possesses superior ability in producing fibers with dimensions similar to the ECM fibers, and the fibers could be engineered into 3D scaffolds that mimic the native ECM morphology. Second, the interconnected pores in the scaffold facilitate cell attachment as well as oxygen/nutrients transport. Moreover, the fibers could be tailored to diverse components, structure and orientation, therefore adjusting the biocompatibility/biodegradability, pore size, and mechanical properties, in adapting to specific target tissues.16,77 A large number of researches have been carried out using aligned nanofibers to manipulate cell morphology, direct cell migration, and guide neurites extension.133137

Apart from such structural regulation, incorporation of certain chemical ingredients generates

additional functions. For example, Elisseeff et al. prepared artificial scaffolds composed of PVA nanofibers network incorporated with chondroitin sulfate, which acted as a biological cue.138 The fibers were synthesized through a refined electrospinning platform. Instead of using a flat substrate, fibers were collected into an ethanol bath, which could be further converted into flexible


33

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 34 of 84

morphologies to fit specific tissue defect site. Such artificial scaffold mimicked the native articular cartilage ECM both structurally and chemically. As a result, it was used to support chondrogenesis of goat mesenchymal stem cells in hydrogel-based in vitro culture system and could be implanted in vivo into rat osteochondral defects for tissue repair, as shown in Figure 7A. Up to now, a large variety of natural and synthetic polymers have been used to construct scaffolds equivalents through electrospinning, including silk fibroin, chitosan, gelatin, polylactic acid (PLA), polycaprolactone (PCL), Poly (vinyl alcohol) (PVA), Poly (lactic-co-glycolic acid) (PLGA), and Polyethylene oxide (PEO).139-148 Surface modification could be made by chemical functionalization to enhance cell adhesion, and nanoparticles could be incorporated to bring additional functions such as antibacterial ability through using silver particles.149 These artificial scaffolds facilitate cell adhesion and proliferation and have been employed for repair and regeneration of various target organ/tissues including but not limited to skin, bone, cartilage, and connective tissue.16 In addition, direct encapsulation of cells during fibers spinning process has been proposed as a way of creating fiber-shaped 3D cellular construct or tissues such as blood vessels. This concept has been mainly realized in microfluidic spinning platforms, through which cells could be completely infiltrated throughout the entire, 3D structure in a one-step process. Till now, a variety of hydrogel microfibers have been prepared consisting of alginate, gelatins or supramolecular hydrogel, and cells were successfully embedded and well dispersed.96,114,150 Besides, microfluidic spinning offers spatiotemporal control of fibers component and structure, therefore facilitating reconstruction of complex, spatially anisotropic tissues. For example, by integrating separatelycontrolled multiple laminar flows in a single microfluidic device, cell-laden hydrogel microfibers with pre-designed multi-compartment-hollow morphologies were generated.151 These fibers could then serve as building blocks for weaving or stacking into complex gridding or multi-layer


34

Page 35 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

architectures, as demonstrated in Figure 7B. Moreover, co-encapsulation of different types of cells within separate fiber compartments has been achieved in mimic of natural tissues. Drug delivery. Drug delivery is another biomedical application aspect of bioinspired fiber materials. Silk fibroin matrices or films have been generated through electrospinning and then used as carriers for the release of bioactive molecules.152,153 The merit of the electrospun nanofibrous delivery system lies in their large surface-to-volume ratio, which enables high drug-loading efficiency. Up to now, a large diversity of drugs, including small-molecular (antibiotics or anticancer drugs)154-156 and macromolecular (DNA, RNA, and proteins)157-159 have been studied in fiber-based drug delivery, and their applications mainly embody in wound dressings and local chemotherapy. Incorporation of drug molecules could be achieved through coating the fibers after spinning,157 direct encapsulating in the polymer matrix prior to spinning,153,155,156 or being wrapped by a polymer shell via coaxial spinning.159 The release profile of drug could be adjusted passively through control of fibers component, surface area, and geometry,156-158 or actively through external stimuli including pH variation,160 magnetic fields,161 and light.162 In addition to directly encapsulating drug molecules or particles in the fiber system, Zhou et al. developed a localized, active-targeting drug delivery model by means of a tumor-specific micelle vehicle, in analogy to natural extracellular vesicles.163 As anti-cancer drug doxorubicin (Dox) was loaded inside of the micelle, which was assembled by PCL-PEG copolymer, with surface decoration of folate (FA) ligands. The micelle vehicle was then encapsulated in the core of polymeric nanofibers through coaxial electrospinning. The drug-entrapped micelle could be released sustainably with degradation of the fiber matrix and could be accumulated around tumor tissue through interstitial transport and enhanced permeation and retention (EPR) effect. Moreover, active targeting could be realized through specific binding of FA ligands and the corresponding receptors overexpressed


35

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 36 of 84

on tumor surfaces. Apart from electrospinning, several studies reported using microfluidic-spun fibers as drug carriers by direct entrapping of drug molecules inside the fiber polymer network,164 or in the separated oil compartments encapsulated in the fiber.165 Sensors and actuators. Life activities involve ubiquitous sensing behaviors in response to various internal or external stimuli, through which information is captured and proper responses are actuated, for the purpose of survival and reproduction. The natural sensory system is highly recognized as being well-organized, sensitive, efficient, and robust. Therefore, it offers a biomimetic principle for the design of smart sensors, in order to further develop bio-robotics, organs-on-a-chip platform, and intelligent devices. Although specific sensing behaviors occur at the cellular level, the structural and geometrical properties of the sensing element have been confirmed responsible for signal acquisition, amplification, filtration, and processing.166 Among these, fibrous sensors widely exist in many creatures (such as insects, bat, and marine organisms) for the detection of approaching predators through the perception of air currents, water flow, sound, as well as vibrations.167,168 Inspired by this, artificial polyvinylidene fluoride (PVDF) micro/nanofiber was prepared by drawing of a viscous PVDF/DMF solution through a micropipette, which was equipped with a heating system to accelerate solvent evaporation. The resultant fibers were around 25 μm in diameter and possessed piezo-effective properties as well as good sensibility to flow turbulence. It thus showing prospects in mini/micro-robots systems.169 Zhao et al. got inspiration from mechanical responsive helix flagellum, and developed a force sensor based on helical microfibers produced by microfluidic spinning.101 As shown in Figure 7C, the helical structure let the fiber behave like a micro-spring. When tied with a biocompatible hydrogel film seeded with cardiomyocytes, it showed periodic stretching and contraction behaviors in response to the beating activity of cardiomyocytes. In this manner, the contraction


36

Page 37 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

force and viability of the cardiomyocytes could be monitored in real time, which shed light on the development of “heart-on-a-chip”. Chen et al reported a strain sensor based on stretchable microfibers with beads-on-a-string geometry in analogy with that of the cribellate spider silk.170 Such shape resulted in uneven distribution of microstructures between the beads and strings, therefore causing strain rearrangement along the fiber, as shown in Figure 7Di. The sensitivity of such delicately structured sensor was enhanced compared to uniform fibers. The strain sensor could be well adhered to a kinesiology tape and integrated with a customized chip, and then used to monitor sports activity including squatting and leg lifting (Figure 7Dii). In addition, Zhang et al. reported using electrospun silk membrane as pressure sensor after a carbonized process, which showed high sensitivity, lightweight, good transparency, and skin-like flexibility.171 It could be integrated into wearable electronics for health-monitoring applications. Apart from mechanical sensors, other types of sensors and actuators are also common in natural organisms. For instance, the mammalian olfactory system is a chemical sensor relying on a library of receptors to generate a combinatorial response (or code) for the identification of a large number of odorants. The hair-like cilia in the olfactory epithelium surface contribute to increased interacting surface area and thus detecting sensitivity. In respect to this, Bayindir developed an “artificial nose” composed of an array of hollow-core fibers possessing a photonic band gap. The fibers were generated by a thermal drawing of a polymer/chalcogenide composite preform, which was obtained through rolling of a wave stack structured film. It transduces chemical to optoelectronic signals in a combinatorial, cross-responsive manner, and differentiate specific chemicals through binary logic tagging and pattern recognition.120 Another example is electrospinning of polyacrylonitrile (PAN) fibers as “artificial muscle” actuators, which shows a rapid contraction and elongation behaviors in response to pH variations.77 Besides, optical sensors


37

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 38 of 84

have been created based on colorimetric nanofibers. These fibers could be prepared via doping or decoration of dyes, nanoparticles, as well as functional polymers in the electrospinning process, or through in situ nanocrystal reactions and colloidal self-assembly during microfluidic spinning.111,172,173 Moreover, a multifunctional fiber probe was developed with composite constituent materials and interrogation modalities, which allowed for simultaneous measurements of mechanical, electrical, optical, and fluidic signals.174 This device enabled optogenetic stimulation, neural recording, drug delivery, and showed high potential for creating brain-machine interfaces and manipulating deep-brain neural circuits. Directional liquid transport. Direct liquid transportation has been drawing considerable attention in both daily life supplies and scientific research areas, among which one dimensional (1D) fibers-based system stands out for its potential applications in various frontiers including microfluidics, intelligent materials, and green energy.18 Theoretically, when a droplet on a 1D solid surface is subjected to unbalanced forces acting on its opposite sides, it moves out of its stationary state towards a specific direction. Such cases are often seen in biological fibers, where unbalanced forces are typically originated from a gradient in geometry and/or surface wettability. Notably, cribellate spider silks are characterized by periodic spindle knots with random nanofibrils and joints with aligned fibrils.85 This structure feature generates synergetic effects of surface energy gradient and Laplace pressure difference, which promote directional droplet movement from the joints towards the knots. A similar mechanism has also been revealed in the cactus spine, whose conical shape and heterogeneous microstructures give rise to multiple geometric and wettability effects for continuous water transportation.175 Inspired by this, artificial fibers have been produced with aim of mimicking the multiscale structure and thus functions of those natural fibers.176 By using a sprayable low-viscosity outer fluid and a spinnable high-viscosity inner fluid in a coaxial


38

Page 39 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

electrospinning setup, artificial spider dragline silk was synthesized with a beads-on-a-string structure and showed excellent fog-collection ability.86 Similarly, by combining droplet emulsification and fiber spinning in a single microfluidic device, spindle-knotted microfibers were generated with humidity-responsive water capture ability.111 Based on these systems, further works have been made by assembling multiple fibers into a mesh or membrane to enhance the water capture efficiency.177 In addition, by adding functional components to the spindle-knots, fibers were endowed with switchable wettability manipulation ability through thermal or optical control.111,178 Moreover, by inducing gas cavities and phase separation process, spindle-cavitiesknotted fibers were obtained with enhanced surface energy gradient due to rougher nanostructures in the knots than in the joints (Figure 8Ai-ii).179 This feature, together with light weight and good mechanical strength, endowed the fibers with long-term durability and efficient water-capture ability, as demonstrated in Figure 8Aiii, showing a fiber-network with a total area of 0.079m2 could collect 1L water in 3 hours under a fog flow of 0.408 mL min−1. Apart from individual-fiber transport, multiple fibers could be integrated into a single system for dynamic wetting manipulation through control over spatial interaction of the fibers. These systems are often found in natural biologic fiber arrays or clusters with certain functions, such as in water strider legs for self-removal, shorebird beak for directional liquid transport, and dandelion pappi for efficient liquid capture.180,181 In principle, adjacent fibers would interplay, and their geometry, as well as elastic feature, would generate synergistic effects together with a structural and/or chemical gradient. Therefore, liquid wetting behavior varies in different situations in order to minimize surface energy. Specifically, when a water drop is deposited on two adjacent fibers, the spreading state (complete or partial wetting) and drop shape (bridge, barrel, and column) are determined by geometrical parameters (fiber length and spacing), droplet properties (diameter and


39

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 40 of 84

volume), mechanical parameter (stiffness), as well as surface tension.180 Inspired by this, artificial fiber clusters with asymmetric spaces between neighboring fibers were created through electrospinning and were used for collective, cyclic, and multistep water collection. Furthermore, a large amount of fibers could be assembled into a two-dimensional (2D) surface, and then rendered with chemical anisotropy (and thus wetting gradient) for anisotropic unidirectional transportation. For example, Zheng et al. designed such kind of surface composed of aligned polyester (PET)/chitosan (CHI) fibers through electrospinning, as shown in Figure 8Bi.182 The aligned structure of the fibers caused a disparity of continuous/discontinuous triple-phase contact line (TCL) in cross directions. Therefore, by adjusting the ratio of the hydrophobic (PET) and hydrophilic (CHI) components, the surface could be tailored with strong anisotropy so that droplet spreading was facilitated in the direction parallel to fiber orientation while being hindered in the direction perpendicular to it (Figure 8Bii). Then, a gradient of the hydrophilic component CHI was created in parallel to the fiber’s alignment through a lifting-dissolution process, and droplets on the surface showed decreasing contact angles along the fiber’s orientation (Figure 8Biii). Through such cooperative control of TCL anisotropy and wetting gradient, the surface enabled unidirectional droplet spreading, and could serve as microreactors by inducing individual droplets flowing in opposite directions (Figure 8Biv). Superwettability systems. Superwettability has gained increasing attention in recent years. On one hand, various intriguing wetting behaviors in natural organisms have been deciphered such as the superhydrophobic lotus leaf and the superhydrophilic fish scale.183 On the other hand, these intelligent systems show significant values in a wide range of applications, such as absorption/separation, self-cleaning, and green printing.184-186 Taking inspiration from nature, the principle of constructing superwettability systems largely involves harnessing the multiscale


40

Page 41 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

structures, and an increase of surface roughness would generally enhance the intrinsic lyophilicity or lyophobicity of a solid surface. With regard to this principle, fibrous material provides a good candidate due to its porous feature and easily tunable chemical and structural properties. For example, a polystyrene (PS) film composed of randomly oriented fibers was prepared through electrospinning, with a microstructure of interconnected voids between the fibers.187 Also, nanopores were distributed in the fiber surface due to vapor-induced phase separation. Such multiscale structural features rendered the resultant film with increased surface roughness, therefore showing superhydrophobicity and superoleophilicity for efficient oil adsorption, as shown in Figure 8C. Similarly, through post modification of silica nanoparticles on the electrospun fibers, a nanofibrous membrane was generated with a hierarchical porous structure and superhydrophobic-oleophilic property, and thus being employed in water-oil separation.188 Apart from being applied in selective adsorption and liquid-liquid separation, fabric materials are also promising for liquid repellent usages through construction of the slippery liquid-infused porous surface (SLIPS). Inspired by the slippery pitcher peristome of the carnivorous plant Nepenthes,189 SLIPS surfaces have been designed with a lubricating liquid being locked stably by a sponge-like substrate. The most fascinating point is that it creates a smooth interface to avoid pinning of the liquid contact line, therefore showing the repellent ability for both water and organic liquids. Thus, it is highly expected to creating coating materials in anti-icing or anti-fouling applications, and anti-bacterial instruments.190,191 In this regard, fibrous materials provide a porous structure for liquid infusion and exhibit large specific area to hold the lubricant. As an example, Yin et al. created a liquid-infused polymer fibrous coating to be directly applied to medical devices.129 Fibers were first spun by compressed gas into a substrate to form the porous matrix. Then, lubricant liquid (silicone oil or perfluoropolyethers) was infused through a gravity-driven


41

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 42 of 84

process to create the SLIPS coating. The resulting coating showed anti-bacterial ability, as bacteria slid readily on the tilted SLIPS surface while remained pinned on the surface without lubricant (Figure 8Di-ii). In addition, such coating exhibited good hemocompatibility, as blood cell adhesion was significantly reduced in the slippery surface compared with non-slippery counterparts (Figure 8Diii-iv), therefore eliminating undesired blood coagulation. These results were highly favorable for designing biomedical instruments with antibacterial and antithrombosis performances. Electrical generator. Developing advanced energy-harvesting and storage technologies is vital to meet the rapidly increasing economic growth and energy demand. Apart from using conventional fossil fuels, alternative energy supplies from sustainable and environmentally friendly sources are highly desired. The design of energy-related materials, especially nanostructured materials, has become one of the most intriguing research hotspots in recent years.[17] Nanostructured materials provide large surface areas for electrochemical reactions and generate certain optical and electrical effects to facilitate electron or ion transport.192 Based on this, a variety of nanogenerator devices have been created that convert different forms of energies (mechanical, light, or chemical energy) into electricity.22,193 Artificial silk nanofibers have been explored in designing these systems owing to economic and environmental considerations. For example, Oh et al. introduced a bio-triboelectric generator that contained a silk fibroin film (regenerated through electrospinning), a polyimide (PI) film, and two aluminum foils as a current collector, as shown in Figure 9A.194 Mechanical energy could be converted into electricity after frictional contact between PI and silk due to their electronegativity difference. The large surface area of friction parts led to improved output voltage performances. In addition, the hydrogen


42

Page 43 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

bonding between the peptide blocks contributed to mechanical stiffness and strength of the generator for durable and sustainable usage. Micromotors. Micro/nanomotors have recently gained wide attention. Inspired by natural motors which move autonomously through a spontaneous chemical reaction such as ATP hydrolysis, artificial motors have been designed to convert a certain type of energy input into mechanical movement.195 The motion could be self-propelled via catalytic reactions (typically along with bubble generation).196,197 In this case, a specially designed geometry of the motor is crucial to confine the bubble generation in a certain path so that to generate vital propulsion for fast and powerful movement. In this regard, a tubular motor is an excellent choice. Guan et al. fabricated short TiO2 hollow microfibers combining wet-spinning with a calcination and cutting process.198 Movement of the fibers was driven by photocatalytic decomposition in a liquid media containing hydrogen peroxide. By regulating the fiber diameter and length, bubbles nucleation and growth were confined in the inner surface. Moreover, the occurrence of motion could be dynamically reactivated or stopped by “on/off” switch of UV irradiation, and the speed could be adjusted by changing the UV intensity. Zhao et al. presented a helical-shaped fiber micromotor as a mimic of bacterial flagellum propulsion, based on the decomposition of hydrogen peroxide by Pt metal nanoparticles.199 By combining microfluidic spinning and flow lithography, discrete helical fibers were generated with multicompartment or core-shell structures. The distribution of catalyst Pt nanoparticles could be well controlled so that the fiber could be propelled along a certain trajectory, as shown in Figure 9Bi. Also, by encapsulating magnetic nanoparticles during the fibers generation process, the motors exhibited 3D movement ability driven by an external magnetic field, including clockwise rotation and corkscrew motion, as shown in Figure 9Bii-iii. CONCLUSION AND OUTLOOK


43

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 44 of 84

In this paper, we present a general review of the emerging spinning techniques and functional fiber materials. Starting with the natural spinning process, we took silk spinning as an example, highlighted essential attributes of natural silks, and emphasized the underlying mechanisms of the spinning process. We then summarized the efforts in developing spinning techniques that taking inspiration from natural silk spinning process and other biosynthesized fibers. The core design of these methods was analyzed, from the perspective of mimicking the natural spinning processes in terms of parameter control, as well as mimicking the morphological or functional features of many types of natural fibers. In addition, the intrinsic merits of each approach were outlined, together with the diverse fiber materials derived from these methods. We also demonstrated various application values of functional fiber materials and highlighted recent cutting-edge studies in a wide range of forefront areas including biomedical science, energy, and environmental engineering. However, despite these exciting achievements, there is still much potential for the development of bioinspired fiber spinning. On one hand, in terms of fabricating artificial silks, although we now have a better understanding of the interaction mechanisms between the raw materials, the spinning processing, and the final products, our knowledge is still insufficient, and intricate control over some critical regulatory factors such as carbon dioxide and protons generated by the carbonic anhydrase has not been thoroughly implemented in current spinning methods. On the other hand, in terms of preparing other functional fiber materials, the superiority of artificial spinning approaches lies in their accommodation of flexible designs, which contributes to the fabrication of fibers with controllable components, morphology, and a variety of functions. However, nature offers an endless treasure of inspiration, and various unexplored fiber materials with desired properties and functions, and their related mechanisms remain to be uncovered. Future endeavors should be focused on both fundamental discoveries and technical


44

Page 45 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

improvements. From a scientific perspective, comprehensive investigations on silks as well as other natural fibers need to be continued, with a thorough examination of anatomy and physiology, cellular and genomic information, and even evolutionary constraints. In this way, crucial information can be gathered on the superiority of natural fiber materials, from which inspiration can be drawn to assist in the design of artificial spinning strategies. From a technical perspective, although current spinning methods can facilitate manipulation of several parameters such as pH value and shear force, more complex regulation processes, such as carbonic anhydrase and enzyme actions, also need to be implemented. To this end, microfluidic spinning seems to be the most promising strategy, because an interfacial environment could be better controlled for many physicochemical processes such as self-assembly, different manipulation modules with specific function units could be integrated, and external fields could be introduced if necessary. In addition, with future progress in recombinant technology, expression of large molecule silk proteins in genetically modified organisms would be expected, and it is hoped that artificial silks can be produced with comparable features to natural silks. Moreover, with closer interdisciplinary cooperation between biologists and researchers from many other fields, an increasing range of natural fibers could serve as prototypes. By combining solution spinning with a certain physicochemical process (phase separation, self-assembly or crystallization), various biomimetic fibers with more intricate structures and functions could be manufactured.178,200 Assembly of such fibers into textile woven or 3D materials is highly promising for applications in biomedical, environmental engineering, and energy consumption.201-203 AUTHOR INFORMATION *E-mail: [email protected], *E-mail: [email protected].


45

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 46 of 84

ACKNOWLEDGMENTS This work is supported by the National Key Research and Development Program of China (2017YFA0700404), the National Science Foundation of China (Grant Nos. 21473029 and 51522302), the NSAF Foundation of China (Grant No. U1530260), the Scientific Research Foundation of Southeast University, and the Scientific Research Foundation of Graduate School of Southeast University. The authors declare no competing financial interests.

VOCABULARY spinning, the way of continuously generating fibers by extrusion/drawing a dope solution from a spinneret; wet spinning, extrusion of the spinning dope solution into a liquid bath containing certain coagulant agent; dry spinning, extrusion of the spinning dope solution in an air environment for solvent evaporation; electrospinning, continuously drawing fibers through electrostatic forces; microfluidic spinning, generation of fibers through a 3D coaxial hydrodynamic flow in a microchannel. direct writing spinning, directly depositing the dope through a micronozzle into a coagulant reservoir; direct drawing spinning, drawning a filament readily from a liquid reservoir.


46

Page 47 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

REFERENCES (1) Sutherland, T. D.; Young, J. H.; Weisman, S.; Hayashi, C. Y.; Merritt, D. J. Insect Silk: One Name, Many Materials. Annu. Rev. Entomol. 2010, 55, 171-188. (2) Tao, H.; Kaplan, D. L.; Omenetto, F. G. Silk Materials-A Road to Sustainable High Technology, Adv. Mater. 2012, 24, 2824-2837. (3) Omenetto, F. G.; Kaplan, D. L. New Opportunities for an Ancient Material. Science 2010, 329, 528-531. (4) Koh, L. D.; Cheng, Y.; Teng, C. P.; Khin, Y. W.; Loh, X. J.; Tee, S. Y.; Low, M.; Ye, E.; Yu, H. D.; Zhang, Y. W.; Han, M. Y. Structures, Mechanical Properties and Applications of Silk Fibroin Materials. Prog. Polym. Sci. 2015, 46, 86-110. (5) Eisoldt, L.; Smith, A.; Scheibel, T. Decoding the Secrets of Spider Silk. Mater. Today 2011, 14, 80-86. (6) Hofmann, E.; Krüger, K.; Haynl, C.; Scheibel, T.; Trebbin, M.; Förster, S. Microfluidic Nozzle Device for Ultrafine Fiber Solution Blow Spinning with Precise Diameter Control. Lab Chip 2018, 18, 2225-2234. (7) Raney, Jordan R.; Compton, B. G.; Mueller, J.; Ober, T. J.; Shea, K.; Lewis, J. A. Rotational 3D Printing of Damage-Tolerant Composites with Programmable Mechanics. Proc. Natl. Acad. Sci. U. S. A. 2018, 115, 1198-1203. (8) Yuk, H.; Zhao, X. A New 3D Printing Strategy by Harnessing Deformation, Instability, and Fracture of Viscoelastic Inks. Adv. Mater. 2018, 30, 1704028. (9) Sun, B.; Long, Y. Z.; Zhang, H. D.; Li, M. M.; Duvail, J. L.; Jiang, X. Y.; Yin, H. L. Advances in Three-Dimensional Nanofibrous Macrostructures via Electrospinning. Prog. Polym. Sci. 2014, 39, 862-890.


47

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 48 of 84

(10)Vollrath, F.; Knight, D. P. Liquid Crystalline Spinning of Spider Silk. Nature 2001, 410, 541548. (11)Andersson, M.; Chen, G.; Otikovs, M.; Landreh, M.; Nordling, K.; Kronqvist, N.; Westermark, P.; Jörnvall, H.; Knight, S.; Ridderstrale, Y.; Holm, L.; Meng, Q.; Jaudzems, K.; Chesler, M.; Johansson, J.; Rising, A. Carbonic Anhydrase Generates CO2 and H+ That Drive Spider Silk Formation Via Opposite Effects on the Terminal Domains. PLoS Biol. 2014, 12, e1001921. (12)Heim, M.; Keerl, D.; Scheibel, T. Spider Silk: From Soluble Protein to Extraordinary Fiber. Angew. Chem. Int. Ed. 2009, 48, 3584-3596. (13)Fu, C.; Shao, Z.; Fritz, V. Animal Silks: their Structures, Properties and Artificial Production. Chem. Commun. 2009, 0, 6515-6529. (14)Koeppel, A.; Holland, C. Progress and Trends in Artificial Silk Spinning: A Systematic Review. ACS Biomater. Sci. Eng. 2017, 3, 226-237. (15)Stoddart, A. Spider silk: Spinning an Artificial Yarn. Nat. Rev. Mater. 2017, 2, 17003. (16)Cheng, J.; Jun, Y.; Qin, J.; Lee, S. H. Electrospinning versus Microfluidic Spinning of Functional Fibers for Biomedical Applications. Biomaterials 2017, 114, 121-143. (17)Sun, H.; Zhang, Y.; Zhang, J.; Sun, X.; Peng, H. Energy Harvesting and Storage in 1D Devices. Nat. Rev. Mater. 2017, 2, 17023. (18)Ju, J.; Zheng, Y.; Jiang, L. Bioinspired One-Dimensional Materials for Directional Liquid Transport. Acc. Chem. Res. 2014, 47, 2342-2352. (19)Wu, H.; Huang, Y. A.; Xu, F.; Duan, Y.; Yin, Z. Energy Harvesters for Wearable and Stretchable Electronics: From Flexibility to Stretchability. Adv. Mater. 2016, 28, 9881-9919. (20)Chang, H.; Luo, J.; Gulgunje, P. V.; Kumar, S. Structural and Functional Fibers. Annu. Rev. Mater. Res. 2017, 47, 331-359.


48

Page 49 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(21)Priemel, T.; Degtyar, E.; Dean, M. N.; Harrington, M. J. Rapid Self-Assembly of Complex Biomolecular Architectures during Mussel Byssus Biofabrication. Nat. Commun. 2017, 8, 14539. (22)Fudge, D. S.; Hillis, S.; Levy, N.; Gosline, J. M. Hagfish Slime Threads as a Biomimetic Model for High Performance Protein Fibres. Bioinspir. Biomim. 2010, 5, 035002. (23)Baer, A.; Schmidt, S.; Haensch, S.; Eder, M.; Mayer, G.; Harrington, M. J. Mechanoresponsive Lipid-Protein Nanoglobules Facilitate Reversible Fibre Formation in Velvet Worm Slime. Nat. Commun. 2017, 8, 974. (24)Domigan, L. J.; Andersson, M.; Alberti, K. A.; Chesler, M.; Xu, Q.; Johansson, J.; Rising, A.; Kaplan, D. L. Carbonic Anhydrase Generates a pH Gradient in Bombyx mori Silk Glands. Insect Biochem. Mol. Biol. 2015, 65, 100-106. (25)Terry, A. E.; Knight, D. P.; Porter, D.; Vollrath, F. pH Induced Changes in the Rheology of Silk Fibroin Solution from the Middle Division of Bombyx mori Silkworm. Biomacromolecules 2004, 5, 768-772. (26)Rising, A.; Johansson, J. Toward Spinning Artificial Spider Silk. Nat. Chem. Biol. 2015, 11, 309-315. (27)Jin, H. J.; Kaplan, D. L. Mechanism of Silk Processing in Insects and Spiders. Nature 2003, 424, 1057-1061. (28)Parent, L. R.; Onofrei, D.; Xu, D.; Stengel, D.; Roehling, J. D.; Addison, J. B.; Forman, C.; Amin, S. A.; Cherry, B. R.; Yarger, J. L.; Gianneschi, N. C.; Holland, G. P. Hierarchical Spidroin Micellar Nanoparticles as the Fundamental Precursors of Spider Silks. Proc. Natl. Acad. Sci. U. S. A. 2018, 115, 11507-11512.


49

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 50 of 84

(29)Zhou, L.; Chen, X.; Shao, Z.; Huang, Y.; Knight, D. P. Effect of Metallic Ions on Silk Formation in the Mulberry Silkworm. Bombyx mori. J. Phys. Chem. B 2005, 109, 1693716945. (30)Breslauer, D. N.; Lee, L. P.; Muller, S. J. Simulation of Flow in the Silk Gland. Biomacromolecules 2009, 10, 49-57. (31)Guinea, G. V.; Elices, M.; Real, J. I.; Gutiérrez, S.; Pérez-Rigueiro, J. Reproducibility of the Tensile Properties of Spider (Argiope trifasciata) Silk Obtained by Forced Silking. J. Exp. Zool. 2005, 303A, 37-44. (32)Vollrath, F.; Madsen, B.; Shao, Z. The Effect of Spinning Conditions on the Mechanics of a Spider's Dragline Silk. Proc. R. Soc. Lond. B 2001, 268, 2339-2346. (33)Pérez-Rigueiro, J.; Elices, M.; Llorca, J.; Viney, C. Tensile Properties of Silkworm Silk Obtained by Forced Silking. J. Appl. Polym. Sci. 2001, 82, 1928-1935. (34)Xia, Q.; Guo, Y.; Zhang, Z.; Li, D.; Xuan, Z.; Li, Z.; Dai, F.; Li, Y.; Cheng, D.; Li, R.; Cheng, T.; Jiang, T.; Becquet, C.; Xu, X.; Liu, C.; Zha, X.; Fan, W.; Lin, Y.; Shen, Y.; Jiang, L., et al. Complete Resequencing of 40 Genomes Reveals Domestication Events and Genes in Silkworm (Bombyx). Science 2009, 326, 433-436. (35)Vainker, S. Chinese Silk: A Cultural History; Rutgers Univ. Press: Piscataway, NJ, USA, 2004; pp 50-51. (36)Pratt, A. E. Two Years among New Guinea Cannibals: A Naturalist’s Sojourn among the Aborigines of Unexplored New Guinea; Seeley and Co. Limited: London, UK 1906; pp 266266. (37)Balfour, H. Kite Fishing. Essays and Studies Presented to William Ridgway; Cambridge University Press: Cambridge, UK 1913; pp 587-590.


50

Page 51 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(38)Shao, Z.; Vollrath, F. Surprising Strength of Silkworm Silk. Nature 2002, 418, 741-741. (39)Lee, S. M.; Pippel, E.; Gösele, U.; Dresbach, C.; Qin, Y.; Chandran, C. V.; Bräuniger, T.; Hause, G.; Knez, M. Greatly Increased Toughness of Infiltrated Spider Silk. Science 2009, 324, 488-492. (40)Teulé, F.; Miao, Y. G.; Sohn, B. H.; Kim, Y. S.; Hull, J. J.; Fraser, M. J.; Lewis, R. V.; Jarvis, D. L. Silkworms Transformed with Chimeric Silkworm/Spider Silk Genes Spin Composite Silk Fibers with Improved Mechanical Properties. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 923-928. (41)Tansil, N. C.; Li, Y.; Teng, C. P.; Zhang, S.; Win, K. Y.; Chen, X.; Liu, X. Y.; Han, M. Y. Intrinsically Colored and Luminescent Silk. Adv. Mater. 2011, 23, 1463-1466. (42)Tansil, N. C.; Koh, L. D.; Han, M. Y. Functional Silk: Colored and Luminescent. Adv. Mater. 2012, 24, 1388-1397. (43)Wang, Q.; Wang, C.; Zhang, M.; Jian, M.; Zhang, Y. Feeding Single-Walled Carbon Nanotubes or Graphene to Silkworms for Reinforced Silk Fibers. Nano Lett. 2016, 16, 66956700. (44)Numata, K.; Kaplan, D. L. Silk-based Delivery Systems of Bioactive Molecules. Adv. Drug Deliv. Rev. 2010, 62, 1497-1508. (45)Rockwood, D. N.; Preda, R. C.; Yücel, T.; Wang, X.; Lovett, M. L.; Kaplan, D. L. Materials Fabrication from Bombyx mori Silk Fibroin. Nat. Protoc. 2011, 6, 1612-1631. (46)Omenetto, F. G.; Kaplan, D. L. A New Route for Silk. Nat. Photon. 2008, 2, 641-643. (47)Kim, U. J.; Park, J.; Kim, H. J.; Wada, M.; Kaplan, D. L. Three-Dimensional AqueousDerived Biomaterial Scaffolds from Silk Sibroin. Biomaterials 2005, 26, 2775-2785.


51

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 52 of 84

(48)Seib, F. P.; Pritchard, E. M.; Kaplan, D. L. Self-Assembling Doxorubicin Silk Hydrogels for the Focal Treatment of Primary Breast Cancer. Adv. Funct. Mater. 2013, 23, 58-65. (49)Min, K.; Kim, S.; Kim, S. Deformable and Conformal Silk Hydrogel Inverse Opal. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, 6185-6190. (50)Hong, M. S.; Choi, G. M.; Kim, J.; Jang, J.; Choi, B.; Kim, J. K.; Jeong, S.; Leem, S.; Kwon, H. Y.; Hwang, H. B.; Im, H. G.; Park, J. U.; Bae, B. S.; Jin, J. Biomimetic Chitin-Silk Hybrids: An Optically Transparent Structural Platform for Wearable Devices and Advanced Electronics. Adv. Funct. Mater. 2017, 27, 1705480. (51)Lee, M. C.; Kim, D. K.; Lee, O. J.; Kim, J. H.; Ju, H. W.; Lee, J. M.; Moon, B. M.; Park, H. J.; Kim, D. W.; Kim, S. H.; Park, C. H. Fabrication of Silk Fibroin Film using Centrifugal Casting Technique for Corneal Tissue Engineering. J. Biomed. Mater. Res. B Appl. Biomater. 2016, 104, 508-514. (52)Seib, F. P.; Jones, G. T.; Rnjak-Kovacina, J.; Lin, Y.; Kaplan, D. L. pH-Dependent Anticancer Drug Release from Silk Nanoparticles. Adv. Healthcare Mater. 2013, 2, 1606-1611. (53)Li, L.; Puhl, S.; Meinel, L.; Germershaus, O. Silk Fibroin Layer-by-Layer Microcapsules for Localized Gene Delivery. Biomaterials 2014, 35, 7929-7939. (54)Tsioris, K.; Raja, W. K.; Pritchard, E. M.; Panilaitis, B.; Kaplan, D. L.; Omenetto, F. G. Fabrication of Silk Microneedles for Controlled-Release Drug Delivery. Adv. Funct. Mater. 2012, 22, 330-335. (55)Zhu, B.; Wang, H.; Leow, W. R.; Cai, Y.; Loh, X. J.; Han, M.-Y.; Chen, X. Silk Fibroin for Flexible Electronic Devices. Adv. Mater. 2016, 28, 4250-4265. (56)Chen, J.; Venkatesan, H.; Hu, J. Chemically Modified Silk Proteins. Adv. Eng. Mater. 2018, 20, 1700961.


52

Page 53 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(57)Huang, W.; Ling, S.; Li, C.; Omenetto, F. G.; Kaplan, D. L. Silkworm Silk-Based Materials and Devices Generated Using Bio-nanotechnology. Chem. Soc. Rev., 2018, 47, 6486-6504. (58)Lin, S.; Ryu, S.; Tokareva, O.; Gronau, G.; Jacobsen, M. M.; Huang, W.; Rizzo, D. J.; Li, D.; Staii, C.; Pugno, N. M.; Wong, J. Y.; Kaplan, D. L.; Buehler, M. J. Predictive ModellingBased Design and Experiments for Synthesis and Sspinning of Bioinspired Silk Fibres. Nat. Commun. 2015, 6, 6892. (59)Yan, J.; Zhou, G.; Knight, D. P.; Shao, Z.; Chen, X. Wet-Spinning of Regenerated Silk Fiber from Aqueous Silk Fibroin Solution: Discussion of Spinning Parameters. Biomacromolecules 2010, 11, 1-5. (60)Um, I. C.; Kweon, H. Y.; Lee, K. G.; Ihm, D. W.; Lee, J.-H.; Park, Y. H. Wet Spinning of Silk Polymer I. Effect of Coagulation Conditions on the Morphological Feature of Filament. Int. J. Biol. Macromol. 2004, 34, 89-105. (61)Zhou, G.; Shao, Z.; Knight, D. P.; Yan, J.; Chen, X. Silk Fibers Extruded Artificially from Aqueous Solutions of Regenerated Bombyx mori Silk Fibroin are Tougher than their Natural Counterparts. Adv. Mater. 2009, 21, 366-370. (62)Phillips, D. M.; Drummy, L. F.; Naik, R. R.; Long, H. C. D.; Fox, D. M.; Trulovec, P. C.; Mantz, R. A. Regenerated Silk Fiber Wet Spinning from an Ionic Liquid Solution. J. Mater. Chem. 2005, 15, 4206-4208. (63)Zhang, F.; Lu, Q.; Yue, X.; Zuo, B.; Qin, M.; Li, F.; Kaplan, D. L.; Zhang, X. Regeneration of High-Quality Silk Fibroin Fiber by Wet Spinning from CaCl2-Formic Acid Solvent. Acta Biomater. 2015, 12, 139-145.


53

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 54 of 84

(64)Andersson, M.; Jia, Q.; Abella, A.; Lee, X. Y.; Landreh, M.; Purhonen, P.; Hebert, H.; Tenje, M.; Robinson, C. V.; Meng, Q.; Plaza, G. R.; Johansson, J. A. Rising, Biomimetic Spinning of Artificial Spider Silk from a Chimeric Minispidroin. Nat. Chem. Biol. 2017, 13, 262-264. (65)Otikovs, M.; Andersson, M.; Jia, Q.; Nordling, K.; Meng, Q.; Andreas, L. B.; Pintacuda, G.; Johansson, J.; Rising, A.; Jaudzems, K. Degree of Biomimicry of Artificial Spider Silk Spinning Assessed by NMR Spectroscopy, Angew. Chem. Int. Ed. 2017, 56, 12571-12575. (66)Rathore, O.; Sogah, D. Y. Self-Assembly of Beta-Sheets into Nanostructures by Poly(alanine) Segments Incorporated in Multiblock Copolymers Inspired by Spider Silk. J. Am. Chem. Soc. 2001, 123, 5231-5239. (67)Teulé, F.; Cooper, A. R.; Furin, W. A.; Bittencourt, D.; Rech, E. L.; Brooks, A.; Lewis, R. V. A Protocol for the Production of Recombinant Spider Silk-like Proteins for Artificial Fiber Spinning. Nat. Protoc. 2009, 4, 341-355. (68)Weatherbee-Martin, N.; Xu, L.; Hupe, A.; Kreplak, L.; Fudge, D. S.; Liu, X. Q.; Rainey, J. K. Identification of Wet-Spinning and Post-Spin Stretching Methods Amenable to Recombinant Spider Aciniform Silk. Biomacromolecules 2016, 17, 2737-2746. (69)Fang, G.; Huang, Y.; Tang, Y.; Qi, Z.; Yao, J.; Shao, Z.; Chen, X. Insights into Silk Formation Process: Correlation of Mechanical Properties and Structural Evolution during Artificial Spinning of Silk Fibers. ACS Biomater. Sci. Eng. 2016, 2, 1992-2000. (70)Um, I. C.; Ki, C. S.; Kweon, H. Y.; Lee, K. G.; Ihm, D. W.; Park, Y. H. Wet Spinning of Silk Polymer II. Effect of Drawing on the Structural Characteristics and Properties of Filament. Int. J. Biol. Macromol. 2004, 34, 107-119. (71)Copeland, C. G.; Bell, B. E.; Christensen, C. D.; Lewis, R. V. Development of a Process for the Spinning of Synthetic Spider Silk. ACS Biomater. Sci. Eng. 2015, 1, 577-584.


54

Page 55 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(72)Heidebrecht, A. Production and Characterization of Artificial Spider Silk Fibers with the Same Toughness as Natural Dragline Silk Fibers. Ph.D. Dissertation, Universität Bayreuth, 2016. (73)Ling, S.; Qin, Z.; Li, C.; Huang, W.; Kaplan, D. L.; Buehler, M. J. Polymorphic Regenerated Silk Fibers Assembled through Bioinspired Spinning. Nat. Commun. 2017, 8, 1387. (74)Sun, M.; Zhang, Y.; Zhao, Y.; Shao, H.; Hu, X. The Structure-Property Relationships of Artificial Silk Fabricated by Dry Spinning Process. J. Mater. Chem. 2012, 22, 18372-18379. (75)Zhang, C.; Zhang, Y.; Shao, H.; Hu, X. Hybrid Silk Fibers Dry-Spun from Regenerated Silk Fibroin/Graphene Oxide Aqueous Solutions. ACS Appl. Mater. Interfaces 2016, 8, 3349-3358. (76)Xue, J.; Xie, J.; Liu, W.; Xia, Y. Electrospun Nanofibers: New Concepts, Materials, and Applications. Acc. Chem. Res. 2017, 50, 1976-1987. (77)Lee, D. Y.; Kim, Y.; Lee, S. J.; Lee, M. H.; Lee, J. Y.; Kim, B. Y.; Cho, N. I. Characteristics of Chemo-Mechanically Driven Polyacrylonitrile Fiber Gel Actuators. Mater. Sci. Eng. C 2008, 28, 294-298. (78)Zhang, X.; Reagan, M. R.; Kaplan, D. L. Electrospun Silk Biomaterial Scaffolds for Regenerative Medicine. Adv. Drug Deliv. Rev. 2009, 61, 988-1006. (79)Jin, H. J.; Fridrikh, S. V.; Rutledge, G. C.; Kaplan, D. L. Electrospinning Bombyx mori Silk with Poly (ethylene oxide). Biomacromolecules 2002, 3, 1233-1239. (80)Zarkoob, S.; Eby, R. K.; Reneker, D. H.; Hudson, S. D.; Ertley, D.; Adams, W. W. Structure and Morphology of Electrospun Silk Nanofibers. Polymer 2004, 45, 3973-3977. (81)Min, B. M.; Lee, G.; Kim, S. H.; Nam, Y. S.; Lee, T. S.; Park, W. H. Electrospinning of Silk Fibroin Nanofibers and its Effect on the Adhesion and Spreading of Normal Human Keratinocytes and Fibroblasts in vitro. Biomaterials 2004, 25, 1289-1297.


55

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 56 of 84

(82)Lang, G.; Neugirg, B. R.; Kluge, D.; Fery, A.; Scheibel, T. Mechanical Testing of Engineered Spider Silk Filaments Provides Insights into Molecular Features on a Mesoscale. ACS Appl. Mater. Interfaces 2017, 9, 892-900. (83)Stegmaier, T.; Linke, M.; Planck, H. Bionics in Textiles: Flexible and Translucent Thermal Insulations for Solar Thermal Applications. Phil. Trans. R. Soc. A 2009, 367, 1749-1758. (84)Zhao, Y.; Cao, X.; Jiang, L. Bio-mimic Multichannel Microtubes by a Facile Method. J. Am. Chem. Soc. 2007, 129, 764-765. (85)Gernhardt, M.; Peng, L.; Burgard, M.; Jiang, S.; Förster, B.; Schmalz, H.; Agarwal, S. Tailoring the Morphology of Responsive Bioinspired Bicomponent Fibers. Macromol. Mater. Eng. 2017, 303, 1700248. (86)Zheng, Y.; Bai, H.; Huang, Z.; Tian, X.; Nie, F. Q.; Zhao, Y.; Zhai, J.; Jiang, L. Directional Water Collection on Wetted Spider Silk. Nature 2010, 463, 640-643. (87)Tian, X.; Bai, H.; Zheng, Y.; Jiang, L. Bio-inspired Heterostructured Bead-on-String Fibers That Respond to Environmental Wetting. Adv. Funct. Mater. 2011, 21, 1398-1402. (88)Bai, F.; Wu, J.; Gong, G.; Guo, L. Biomimetic “Cactus Spine” with Hierarchical Groove Structure for Efficient Fog Collection. Adv. Sci. 2015, 2, 1500047. (89)Shang, L.; Cheng, Y.; Zhao, Y. Emerging Droplet Microfluidics. Chem. Rev. 2017, 117, 79648040. (90)Lee, T. Y.; Choi, T. M.; Shim, T. S.; Frijns, R. A. M.; Kim, S. H. Microfluidic Production of Multiple Emulsions and Functional Microcapsules. Lab Chip 2016, 16, 3415-3440. (91)Shang, L.; Fu, F.; Cheng, Y.; Wang, H.; Liu, Y.; Zhao, Y.; Gu, Z. Photonic Crystal Microbubbles as Suspension Barcodes. J. Am. Chem. Soc. 2015, 137, 15533-15539.


56

Page 57 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(92)Zhao, Y.; Shum, H. C.; Chen, H.; Adams, L. L. A.; Gu, Z.; Weitz, D. A. Microfluidic Generation of Multifunctional Quantum Dot Barcode Particles. J. Am. Chem. Soc. 2011, 133, 8790-8793. (93)Shi, X.; Ostrovidov, S.; Zhao, Y.; Liang, X.; Kasuya, M.; Kurihara, K.; Nakajima, K.; Bae, H.; Wu, H.; Khademhosseini, A. Microfluidic Spinning of Cell-Responsive Grooved Microfibers. Adv. Funct. Mater. 2015, 25, 2250-2259. (94)Zhao, Y.; Shang, L.; Cheng, Y.; Gu, Z. Spherical Colloidal Photonic Crystals. Acc. Chem. Res. 2014, 47, 3632-3642. (95)Yu, Y.; Shang, L.; Guo, J.; Wang, J.; Zhao, Y. Design of Capillary Microfluidics for Spinning Cell-Laden Microfibers. Nat. Protoc. 2018, 13, 2557-2579. (96)Jun, Y.; Kang, E.; Chae, S.; Lee, S. H. Microfluidic Spinning of Micro- and Nano-scale Fibers for Tissue Engineering. Lab Chip 2014, 14, 2145-2160. (97)Daniele, M. A.; Radom, K.; Ligler, F. S.; Adams, A. A. Microfluidic Fabrication of Multiaxial Microvessels via Hydrodynamic Shaping. RSC Adv. 2014, 4, 23440-23446. (98)Oh, J.; Kim, K.; Won, S. W.; Cha, C.; Gaharwar, A. K.; Selimović, Š.; Bae, H.; Lee, K. H.; Lee, D. H.; Lee, S.-H.; Khademhosseini, A. Microfluidic Fabrication of Cell Adhesive Chitosan Microtubes. Biomed. Microdevices, 2013, 15, 465-472. (99)Hwang, C. M.; Khademhosseini, A.; Park, Y.; Sun, K.; Lee, S.-H. Microfluidic Chip-Based Fabrication of PLGA Microfiber Scaffolds for Tissue Engineering. Langmuir 2008, 24, 68456851. (100) Bonhomme, O.; Leng, J.; Colin, A. Microfluidic Wet-Spinning of Alginate Microfibers: a Theoretical Analysis of Fiber Formation. Soft Matter 2012, 8, 10641-10649.


57

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 58 of 84

(101) Yu, Y.; Fu, F.; Shang, L.; Cheng, Y.; Gu, Z.; Zhao, Y. Bioinspired Helical Microfibers from Microfluidics. Adv. Mater. 2017, 29, 1605765. (102) Martel, A.; Burghammer, M.; Davies, R. J.; Cola, E. D.; Vendrely, C.; Riekel, C. Silk Fiber Assembly Studied by Synchrotron Radiation SAXS/WAXS and Raman Spectroscopy. J. Am. Chem. Soc. 2008, 130, 17070-17074. (103) Rammensee, S.; Slotta, U.; Scheibel, T.; Bausch, A. R. Assembly Mechanism of Recombinant Spider Silk Proteins. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 6590-6595. (104) Kinahan, M. E.; Filippidi, E.; Köster, S.; Hu, X.; Evans, H. M.; Pfohl, T.; Kaplan, D. L.; Wong, J. Tunable Silk: Using Microfluidics to Fabricate Silk Fibers with Controllable Properties. Biomacromolecules 2011, 12, 1504-1511. (105) Li, D.; Jacobsen, M. M.; Rim, N. G.; Backman, D.; Kaplan, D. L.; Wong, J. Y. Introducing Biomimetic Shear and Ion Gradients to Microfluidic Spinning Improves Silk Fiber Strength. Biofabrication 2017, 9, 025025. (106) Renberg, B.; Andersson-Svahn, H.; Hedhammar, M. Mimicking Silk Spinning in a Microchip. Sensor. Actuat. B 2014, 195, 404-408. (107) Cheng, J.; Park, D. Y.; Jun, Y.; Lee, J. S.; Hyun, J.; Lee, S. H. Biomimetic Spinning of Silk Fibers and in situ Cell Encapsulation. Lab Chip 2016, 16, 2654-2661. (108) Mittal, N.; Ansari, F.; Gowda.V, K.; Brouzet, C.; Chen, P.; Larsson, P. T.; Roth, S. V.; Lundell, F.; Wågberg, L.; Kotov, N. A.; Söderberg, L. D. Multiscale Control of Nanocellulose Assembly: Transferring Remarkable Nanoscale Fibril Mechanics to Macroscale Fibers. ACS Nano. 2018, 12, 6378-6388. (109) Haynl, C.; Hofmann, E.; Pawar, K.; Förster, S.; Scheibel, T. Microfluidics-Produced Collagen Fibers Show Extraordinary Mechanical Properties. Nano. Lett. 2016, 16, 5917-5922.


58

Page 59 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(110) Kang, E.; Jeong, G. S.; Choi, Y. Y.; Lee, K. H.; Khademhosseini, A.; Lee, S. H. Digitally Tunable Physicochemical Coding of Material Composition and Topography in Continuous Microfibres. Nat. Mater. 2011, 10, 877-883. (111) Cheng, Y.; Zheng, F.; Lu, J.; Shang, L.; Xie, Z.; Zhao, Y.; Chen, Y.; Gu, Z. Bioinspired Multicompartmental Microfibers from Microfluidics. Adv. Mater. 2014, 26, 5184-5190. (112) Shang, L.; Fu, F.; Cheng, Y.; Yu, Y.; Wang, J.; Gu, Z.; Zhao, Y. Bioinspired Multifunctional Spindle-Knotted Microfibers from Microfluidics. Small 2017, 13, 1600286. (113) Xie, R.; Xu, P.; Liu, Y.; Li, L.; Luo, G.; Ding, M.; Liang, Q. Necklace-Like Microfibers with Variable Knots and Perfusable Channels Fabricated by an Oil-Free Microfluidic Spinning Process. Adv. Mater. 2018, 30, 1705082. (114) Yu, Y.; Wen, H.; Ma, J.; Lykkemark, S.; Xu, H.; Qin, J. Flexible Fabrication of Biomimetic Bamboo-Like Hybrid Microfibers. Adv. Mater. 2014, 26, 2494-2499. (115) Stark, M.; Grip, S.; Rising, A.; Hedhammar, M.; Engström, W.; Hjälm, G.; Johansson, J. Macroscopic Fibers Self-Assembled from Recombinant Miniature Spider Silk Proteins. Biomacromolecules 2007, 8, 1695-1701. (116) Wu, Y.; Shah, D. U.; Liu, C.; Yu, Z.; Liu, J.; Ren, X.; Rowland, M. J.; Abell, C.; Ramage, M. H.; Scherman, O. A. Bioinspired Supramolecular Fibers Drawn from a Multiphase SelfAssembled Hydrogel. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, 8163-8168. (117) Kohler, D.; Schneider, M.; Krüger, M.; Lehr, C. M.; Möhwald, H.; Wang, D. TemplateAssisted Polyelectrolyte Encapsulation of Nanoparticles into Dispersible, Hierarchically Nanostructured Microfibers. Adv. Mater. 2011, 23, 1376-1379.


59

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 60 of 84

(118) Toivonen, M. S.; Kurki-Suonio, S.; Wagermaier, W.; Hynninen, V.; Hietala, S.; Ikkala, O. Interfacial Polyelectrolyte Complex Spinning of Cellulose Nanofibrils for Advanced Bicomponent Fibers. Biomacromolecules 2017, 18, 1293-1301. (119) Leong, M. F.; Toh, J. K. C.; Du, C.; Narayanan, K.; Lu, H. F.; Lim, T. C.; Wan, A. C. A.; Ying, J. Y. Patterned Prevascularised Tissue Constructs by Assembly of Polyelectrolyte Hydrogel Fibres. Nat. Commun. 2013, 4, 2353. (120) Yildirim, A.; Vural, M.; Yaman, M.; Bayindir, M. Bioinspired Optoelectronic Nose with Nanostructured Wavelength-Scalable Hollow-Core Infrared Fibers. Adv. Mater. 2011, 23, 1263-1267. (121) Shabahang, S.; Tao, G.; Kaufman, J. J.; Qiao, Y.; Wei, L.; Bouchenot, T.; Gordon, A. P.; Fink, Y.; Bai, Y.; Hoy, R. S.; Abouraddy, A. F. Controlled Fragmentation of Multimaterial Fibres and Films via Polymer Cold-Drawing. Nature 2016, 534, 529-533. (122) Truby, R. L.; Lewis, J. A. Printing Soft Matter in Three Dimensions. Nature 2016, 540, 371-378. (123) Ghosh, S.; Parker, S. T.; Wang, X.; Kaplan, D. L.; Lewis, J. A. Direct-Write Assembly of Microperiodic Silk Fibroin Scaffolds for Tissue Engineering Applications. Adv. Funct. Mater. 2008, 18, 1883-1889. (124) Sun, L.; Parker, S. T.; Syoji, D.; Wang, X.; Lewis, J. A.; Kaplan, D. L. Direct-Write Assembly of 3D Silk/Hydroxyapatite Scaffolds for Bone Co-Cultures. Adv. Healthcare Mater. 2012, 1, 729-735. (125) Brown, T. D.; Dalton, P. D.; Hutmacher, D. W. Melt Electrospinning Today: An Opportune Time for an Emerging Polymer Process. Prog. Polym. Sci. 2016, 56, 116-166.


60

Page 61 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(126) Wunner, F. M.; Wille, M.‐L.; Noonan, T. G.; Bas, O.; Dalton, P. D.; De‐Juan‐Pardo, E. M.; Hutmacher, D. W. Melt Electrospinning Writing of Highly Ordered Large Volume Scaffold Architectures, Adv. Mater. 2018, 30, 1706570. (127) Chen, P.; Xu, Y.; He, S.; Sun, X.; Guo, W.; Zhang, Z.; Qiu, L.; Li, J.; Chen, D.; Peng, H. Biologically Inspired, Sophisticated Motions from Helically Assembled, Conducting Fibers. Adv. Mater. 2015, 27, 1042-1047. (128) Zhang, J.; Feng, W.; Zhang, H.; Wang, Z.; Calcaterra, H. A.; Yeom, B.; Hu, P. A.; Kotov, N. A. Multiscale Deformations Lead to High Toughness and Circularly Polarized Emission in Helical Nacre-like Fibres. Nat. Commun. 2016, 7, 10701. (129) Yuan, S.; Li, Z.; Song, L.; Shi, H.; Luan, S.; Yin, J. Liquid-Infused Poly(styrene-bisobutylene-b-styrene) Microfiber Coating Prevents Bacterial Attachment and Thrombosis. ACS Appl. Mater. Interfaces 2016, 8, 21214-21220. (130) Tokarev, A.; Trotsenko, O.; Griffiths, I. M.; Stone, H. A.; Minko, S. Magnetospinning of Nano- and Microfibers. Adv. Mater. 2015, 27, 3560-3565. (131) Tokarev, A.; Trotsenko, O.; Asheghali, D.; Griffiths, I. M.; Stone, H. A.; Minko, S. Reactive Magnetospinning of Nano- and Microfibers. Angew. Chem. Int. Ed. 2015, 54, 1361313616. (132) Lutolf, M. P.; Hubbell, J. A. Synthetic Biomaterials as Instructive Extracellular Microenvironments for Morphogenesis in Tissue Engineering. Nat. Biotechnol. 2005, 23, 4755. (133) Barnes, C. P.; Sell, S. A.; Boland, E. D.; Simpson, D. G.; Bowlin, G. L. Nanofiber Technology: Designing the Next Generation of Tissue Engineering Scaffolds. Adv. Drug Deliv. Rev. 2007, 59, 1413-1433.


61

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 62 of 84

(134) Shah, S.; Yin, P. T.; Uehara, T. M.; Chueng, S. T. D.; Yang, L.; Lee, K. B. Guiding Stem Cell Differentiation into Oligodendrocytes Using Graphene-Nanofiber Hybrid Scaffolds. Adv. Mater. 2014, 26, 3673-3680. (135) Zuidema, J. M.; Hyzinski-García, M. C.; Vlasselaer, K. V.; Zaccor, N. W.; Plopper, G. E.; Mongin, A. A.; Gilbert, R. J. Enhanced GLT-1 Mediated Glutamate Uptake and Migration of Primary Astrocytes Directed by Fibronectin-Coated Electrospun Poly-L-lactic Acid Fibers. Biomaterials 2014, 35, 1439-1449. (136) Liu, Y.; Sun, Y.; Yan, H.; Liu, X.; Zhang, W.; Wang, Z.; Jiang, X. Electrospun Fiber Template for Replica Molding of Microtopographical Neural Growth Guidance. Small 2012, 8, 676-681. (137) Jia, C.; Yu, D.; Lamarre, M.; Leopold, P. L.; Teng, Y. D.; Wang, H. Patterned Electrospun Nanofiber Matrices Via Localized Dissolution: Potential for Guided Tissue Formation. Adv. Mater. 2014, 26, 8192-8197. (138) Coburn, J. M.; Gibson, M.; Monagle, S.; Patterson, Z.; Elisseeff, J. H. Bioinspired Nanofibers Support Chondrogenesis for Articular Cartilage Repair. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 10012-10017. (139) Kundu, B.; Kurland, N. E.; Bano, S.; Patra, C.; Engel, F. B.; Yadavalli, V. K.; Kundu, S. C. Silk Proteins for Biomedical Applications: Bioengineering Perspectives. Prog. Polym. Sci. 2014, 39, 251-267. (140) Cheng, L.; Sun, X.; Zhao, X.; Wang, L.; Yu, J.; Pan, G.; Li, B.; Yang, H.; Zhang, Y.; Cui, W. Surface Biofunctional Drug-Loaded Electrospun Fibrous Scaffolds for Comprehensive Repairing Hypertrophic Scars. Biomaterials 2016, 83, 169-181.


62

Page 63 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(141) Binan, L.; Tende, C.; Crescenzo, G. D.; Ayoubi, R. E.; Ajji, A.; Jolicoeur, M. Differentiation of Neuronal Stem Cells into Motor Neurons Using Electrospun Poly-L-lactic Acid/Gelatin Scaffold. Biomaterials 2014, 35, 664-674. (142) Sun, B.; Long, Y. Z.; Zhang, H. D.; Li, M. M.; Duvail, J. L.; Jiang, X. Y.; Yin, H. L. Advances in Three-Dimensional Nanofibrous Macrostructures via Electrospinning. Prog. Polym. Sci. 2014, 39, 862-890. (143) Yang, X.; Yang, J.; Wang, L.; Ran, B.; Jia, Y.; Zhang, L.; Yang, G.; Shao, H.; Jiang. X. Pharmaceutical Intermediate-Modified Gold Nanoparticles: Against Multidrug-Resistant Bacteria and Wound-Healing Application via an Electrospun Scaffold. ACS Nano 2017, 11, 5737-5745. (144) He, M.; Jiang, H.; Wang, R.; Xie, Y.; Zhao, C. Fabrication of Metronidazole Loaded Poly (ε-caprolactone)/Zein Core/Shell Nanofiber Membranes via Coaxial Electrospinning for Guided Tissue Regeneration. J. Colloid. Interface Sci. 2017, 490, 270-278. (145) Yi, B.; Zhang, H.; Yu, Z.; Yuan, H.; Wang, X.; Zhang, Y. Fabrication of High Performance Silk Fibroin Fibers via Stable Jet Electrospinning for Potential use in Anisotropic Tissue Regeneration. J. Mater. Chem. B 2018, 6, 3934-3945. (146) Yao, Q.; Cosme, J. G. L.; Xu, T.; Miszuk, J. M.; Picciani, P. H. S.; Fong, H.; Sun, H. Three Dimensional Electrospun PCL/PLA Blend Nanofibrous Scaffolds with Significantly Improved Stem Cells Osteogenic Differentiation and Cranial Bone Formation. Biomaterials 2017, 115, 115-127. (147) Gao, S.; Chen, M.; Wang, P.; Li, Y.; Yuan, Z.; Guo, W.; Zhang, Z.; Zhang, X.; Jing, X.; Li, X.; Liu, S.; Sui, X.; Xi, T.; Guo, Q. An Electrospun Fiber Reinforced Scaffold Promotes


63

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 64 of 84

Total Meniscus Regeneration in Rabbit Meniscectomy Model. Acta Biomater. 2018, 73, 127140. (148) Shrestha, S.; Shrestha, B. K.; Kim, J. I.; Ko. S. W.; Park, C. H.; Kim, C. S. Electrodeless Coating Polypyrrole on Chitosan Grafted Polyurethane with Functionalized Multiwall Carbon Nanotubes Electrospun Scaffold for Nerve Tissue Engineering. Carbon 2018, 136, 430-443. (149) Shi, Q.; Vitchuli, N.; Nowak, J.; Noar, J.; Caldwell, J. M.; Breidt, F.; Bourham, M.; McCord, M.; Zhang, X. One-Step Synthesis of Silver Nanoparticle-Filled Nylon 6 Nanofibers and their Antibacterial Properties. J. Mater. Chem. 2011, 21, 10330-10335. (150) Kang, A.; Park, J.; Ju, J.; Jeong, G. S.; Lee, S.-H. Cell Encapsulation via Microtechnologies. Biomaterials 2014, 35, 2651-2663. (151) Cheng, Y.; Yu, Y.; Fu, F.; Wang, J.; Shang, L.; Gu, Z.; Zhao, Y. Controlled Fabrication of Bioactive Microfibers for Creating Tissue Constructs Using Microfluidic Techniques. ACS Appl. Mater. Interfaces 2016, 8, 1080-1086. (152) Sridhar, R.; Lakshminarayanan, R.; Madhaiyan, K.; Barathi, V. A.; Lim, K. H. C.; Ramakrishna, S. Electrosprayed Nanoparticles and Electrospun Nanofibers based on Natural Materials: Applications in Tissue Regeneration, Drug Delivery and Pharmaceuticals. Chem. Soc. Rev. 2015, 44, 790-814. (153) Pignatelli, C.; Perotto, G.; Nardini, M.; Cancedda, R.; Mastrogiacomo, M.; Athanassiou, A. Electrospun Silk Fibroin Fibers for Storage and Controlled Release of Human Platelet Lysate. Acta Biomater. 2018, 73, 365-376. (154) Hu, X.; Liu, S.; Zhou, G.; Huang, Y.; Xie, Z.; Jing, X. Electrospinning of Polymeric Nanofibers for Drug Delivery Applications. J. Control. Release 2014, 85, 12-21.


64

Page 65 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(155) Zhao, X.; Yuan, Z.; Yildirimer, L.; Zhao, J.; Lin, Z. Y.; Cao, Z.; Pan, G.; Cui, W. Tumor‐ Triggered Controlled Drug Release from Electrospun Fibers Using Inorganic Caps for Inhibiting Cancer Relapse. Small 2015, 11, 4284-4291. (156) Zhang, Z.; Tang, J.; Wang, H.; Xia, Q.; Xu, S.; Han, C. C. Controlled Antibiotics Release System through Simple Blended Electrospun Fibers for Sustained Antibacterial Effects. ACS Appl. Mater. Interfaces 2015, 7, 26400-26404. (157) Zhang, J.; Zheng, T.; Alarçin, E.; Byambaa, B.; Guan, X.; Ding, J.; Zhang, Y. S.; Li, Z. Porous Electrospun Fibers with Self-Sealing Functionality: An Enabling Strategy for Trapping Biomacromolecules. Small 2017, 13, 1701949. (158) Pinese, C.; Lin, J.; Milbreta, U.; Li, M.; Wang, Y.; Leong, K. W.; Chew, S. Y. Sustained Delivery of siRNA/Mesoporous Silica Nanoparticle Complexes from Nanofiber Scaffolds for Long-Term Gene Silencing. Acta Biomater. 2018, 76, 164-177. (159) Nagase, K.; Nagumo, Y.; Kim, M.; Kim, H.‐J.; Kyung, H.‐W.; Chung, H.‐J.; Sekine, H.; Shimizu, T.; Kanazawa, H.; Okano, T.; Lee, S.‐J.; Yamato, M. Local Release of VEGF Using Fiber Mats Enables Effective Transplantation of Layered Cardiomyocyte Sheets. Macromol. Biosci. 2017, 17, 1700013. (160) Yang, C.; Yu, D.-G.; Pan, D.; Liu, X.-K.; Wang, X.; Bligh, S. W. A.; Williams, G. R. Electrospun pH-sensitive Core-Shell Polymer Nanocomposites Fabricated Using a Tri-axial Process. Acta Biomater. 2016, 35, 77-86. (161) Perera, A. S.; Zhang, S.; Homer-Vanniasinkam, S.; Coppens, M.-O.; Edirisinghe, M. Polymer-Magnetic Composite Fibers for Remote-Controlled Drug Release, ACS Appl. Mater. Interfaces 2018, 10, 15524-15531.


65

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 66 of 84

(162) Askes, S. H. C.; Reddy, G. U.; Wyrwa, R.; Bonnet, S.; Schiller, A. Red Light-Triggered CO Release from Mn2(CO)10 Using Triplet Sensitization in Polymer Nonwoven Fabrics. J. Am. Chem. Soc. 2017, 139, 15292-15295. (163) Yang, G.; Wang, J.; Wang, Y.; Li, L.; Guo, X.; Zhou, S. An Implantable Active-Targeting Micelle-in-Nanofiber Device for Efficient and Safe Cancer Therapy. ACS Nano 2015, 9, 11611174. (164) Ahn, S. Y.; Mun, C. H.; Lee, S. H. Microfluidic Spinning of Fibrous Alginate Carrier having Highly Enhanced Drug Loading Capability and Delayed Release Profile. RSC Adv. 2015, 5, 15172-15181. (165) He, X.-H.; Wang, W.; Deng, K.; Xie, R.; Ju, X.-J.; Liu, Z.; Chu, L.-Y. Microfluidic Fabrication of Chitosan Microfibers with Controllable Internals from Tubular to Peapod-like Structures, RSC Adv. 2015, 5, 928-936. (166) Johnson, E. A. C.; Bonser, R. H. C.; Jeronimidis, G. Recent Advances in Biomimetic Sensing Technologies. Phil. Trans. R. Soc. A 2009, 367, 1559-1569. (167) Dehnhardt, G.; Mauck, B.; Bleckmann, H. Seal Whiskers Detect Water Movements. Nature 1998, 394, 235-236. (168) Fratzl, P.; Barth, F. G. Biomaterial Systems for Mechanosensing and Actuation. Nature 2009, 462, 442-448. (169) Li, F.; Liu, W.; Stefanini, C.; Fu, X.; Dario, P. A Novel Bioinspired PVDF Micro/Nano Hair Receptor for a Robot Sensing System. Sensors 2010, 10, 994-1011. (170) Liu, Z.; Qi, D.; Hu, G.; Wang, H.; Jiang, Y.; Chen, G.; Luo, Y.; Loh, X. J.; Liedberg, B.; Chen, X. Surface Strain Redistribution on Structured Microfibers to Enhance Sensitivity of Fiber-Shaped Stretchable Strain Sensors. Adv. Mater. 2017, 29, 1704229.


66

Page 67 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(171) Wang, Q.; Jian, M.; Wang, C.; Zhang, Y. Carbonized Silk Nanofiber Membrane for Transparent and Sensitive Electronic Skin. Adv. Funct. Mater. 2017, 27, 1605657. (172) Schoolaert, E.; Hoogenboom, R.; Clerck, K. D. Colorimetric Nanofibers as Optical Sensors. Adv. Funct. Mater. 2017, 27, 1702646. (173) Zhang, Y.; Wang, C. F.; Chen, L.; Chen, S.; Ryan, A. J. Microfluidic-Spinning-Directed Microreactors Toward Generation of Multiple Nanocrystals Loaded Anisotropic Fluorescent Microfibers. Adv. Funct. Mater. 2015, 25, 7253-7262. (174) Canales, A.; Jia, X.; Froriep, U. P.; Koppes, R. A.; Tringides, C. M.; Selvidge, J.; Lu, C.; Hou, C.; Wei, L.; Fink, Y.; Anikeeva, P. Multifunctional Fibers for Simultaneous Optical, Electrical and Chemical Interrogation of Neural Circuits in vivo. Nat. Biotechnol. 2015, 33, 277-284. (175) Ju, J.; Bai, H.; Zheng, Y.; Zhao, T.; Fang, R.; Jiang, L. A Multi-Structural and MultiFunctional Integrated Fog Collection System in Cactus. Nat. Commun. 2012, 3, 1247. (176) Bai, H.; Ju, J.; Zheng, Y.; Jiang, L. Functional Fibers with Unique Wettability Inspired by Spider Silks. Adv. Mater. 2012, 24, 2786-2791. (177) He, X. H.; Wang, W.; Liu, Y. M.; Jiang, M. Y.; Wu, F.; Deng, K.; Liu, Z.; Ju, X. J.; Xie, R.; Chu, L. Y. Microfluidic Fabrication of Bio-Inspired Microfibers with Controllable Magnetic Spindle-Knots for 3D Assembly and Water Collection. ACS Appl. Mater. Interfaces 2015, 7, 17471-17481. (178) Shang, L.; Wang, Y.; Yu, Y.; Wang, J.; Zhao, Z.; Xu, H.; Zhao, Y. Bio-Inspired StimuliResponsive Graphene Oxide Fibers from Microfluidics. J. Mater. Chem. A 2017, 5, 1502615030.


67

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 68 of 84

(179) Tian, Y.; Zhu, P.; Tang, X.; Zhou, C.; Wang, J.; Kong, T.; Xu, M.; Wang, L. Large-Scale Water Collection of Bioinspired Cavity-Microfibers. Nat. Commun. 2017, 8, 1080. (180) Duprat, C.; Protière, S.; Beebe, A. Y.; Stone, H. A. Wetting of Flexible Fibre Arrays. Nature 2012, 482, 510-513. (181) Wang, P.; Bian, R.; Meng, Q.; Liu, H.; Jiang, L. Bioinspired Dynamic Wetting on Multiple Fibers. Adv. Mater. 2017, 29, 1703042. (182) Zhang, M.; Wang, L.; Hou, Y.; Shi, W.; Feng, S.; Zheng, Y. Controlled Smart Anisotropic Unidirectional Spreading of Droplet on a Fibrous Surface. Adv. Mater. 2015, 27, 5057-5062. (183) Liu, M.; Wang, S.; Jiang, L.; Zheng, Y. Nature-Inspired Superwettability Systems. Nat. Rev. Mater. 2017, 2, 17036. (184) Wang, J.; Sun, L.; Zou, M.; Gao, W.; Liu, C.; Shang, L.; Gu, Z.; Zhao, Y. Bioinspired Shape-Memory Graphene Film with Tunable Wettability. Sci. Adv. 2017, 3, e1700004. (185) Wu, L.; Dong, Z.; Kuang, M.; Li, Y.; Li, F.; Jiang, L.; Song, Y. Printing Patterned Fine 3D Structures by Manipulating the Three Phase Contact Line. Adv. Funct. Mater. 2015, 25, 22372242. (186) Yao, X.; Song, Y.; Jiang, L. Applications of Bio-Inspired Special Wettable Surfaces. Adv. Mater. 2011, 23, 719-734. (187) Wu, J.; Wang, N.; Wang, L.; Dong, H.; Zhao, Y.; Jiang, L. Electrospun Porous Structure Fibrous Film with High Oil Adsorption Capacity. ACS Appl. Mater. Interfaces 2012, 4, 32073212. (188) Tang, X.; Si, Y.; Ge, J.; Ding, B.; Liu, L.; Zheng, G.; Luo, W.; Yu, J. In situ Polymerized Superhydrophobic and Superoleophilic Nanofibrous Membranes for Gravity Driven OilWater Separation. Nanoscale 2013, 5, 11657-11664.


68

Page 69 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(189) Chen, H.; Zhang, P.; Zhang, L.; Liu, H.; Jiang, Y.; Zhang, D.; Han, Z.; Jiang, L. Continuous Directional Water Transport on The Peristome Surface of Nepenthes alata. Nature 2016, 532, 85-89. (190) Wong, T. S.; Kang, S. H.; Tang, S. K. Y.; Smythe, E. J.; Hatton, B. D.; Grinthal, A.; Aizenberg, J. Bioinspired Self-Repairing Slippery Surfaces with Pressure-Stable Omniphobicity. Nature 2011, 477, 443-447. (191) Leslie, D. C.; Waterhouse, A.; Berthet, J. B.; Valentin, T. M.; Watters, A. L.; Jain, A.; Kim, P.; Hatton, B. D.; Nedder, A.; Donovan, K.; Super, E. H.; Howell, C.; Johnson, C. P.; Vu, T. L.; Bolgen, D. E.; Rifai, S.; Hansen, A. R.; Aizenberg, M.; Super, M.; Aizenberg, J.; Ingber, D. E. A Bioinspired Omniphobic Surface Coating on Medical Devices Prevents Thrombosis and Biofouling. Nat. Biotechnol. 2014, 32, 1134-1140. (192) Balaya, P. Size Effects and Nanostructured Materials for Energy Applications. Energy Environ. Sci. 2008, 1, 645-654. (193) Wang, X.; Song, J.; Liu, J.; Wang, Z. L. Direct-Current Nanogenerator Driven by Ultrasonic Waves. Science 2007, 316, 102-105. (194) Kim, H. J.; Kim, J. H.; Jun, K. W.; Kim, J. H.; Seung, W. C.; Kwon, O. H.; Park, J. Y.; Kim, S. W.; Oh, I. K. Silk Nanofiber-Networked Bio-Triboelectric Generator: Silk Bio-TEG. Adv. Energy Mater. 2016, 6, 1502329. (195) Singh, V. V.; Soto, F.; Kaufmann, K.; Wang, J. Micromotor-Based Energy Generation. Angew. Chem. Int. Ed. 2015, 54, 6896-6899. (196) Gao, W.; Wang, J. The Environmental Impact of Micro/Nanomachines: A Review. ACS Nano 2014, 8, 3170-3180.


69

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 70 of 84

(197) de Ávila, B. E. F.; Angsantikul, P.; Li, J.; Lopez-Ramirez, M. A.; Ramírez-Herrera, D. E.; Thamphiwatana, S.; Chen, C.; Delezuk, J.; Samakapiruk, R.; Ramez, V.; Obonyo, M.; Zhang, L.; Wang, J. Micromotor-Enabled Active Drug Delivery for in vivo Treatment of Stomach Infection. Nat. Commun. 2017, 8, 272. (198) Mou, F.; Li, Y.; Chen, C.; Li, W.; Yin, Y.; Ma, H.; Guan, J. Single-Component TiO2 Tubular Microengines with Motion Controlled by Light-Induced Bubbles. Small 2015, 11, 2564-2570. (199) Yu, Y.; Shang, L.; Gao, W.; Zhao, Z.; Wang, H.; Zhao, Y. Microfluidic Lithography of Bioinspired Helical Micromotors. Angew. Chem. Int. Ed. 2017, 56, 12127-12131. (200) Cui, Y.; Gong, H.; Wang, Y.; Li, D.; Bai, H. A Thermally Insulating Textile Inspired by Polar Bear Hair. Adv. Mater. 2018, 30, 1706807. (201) Sun, T.; Shi, Q.; Huang, Q.; Wang, H.; Xiong, X.; Hu, C.; Fukuda, T. Magnetic Alginate Microfibers as Scaffolding Elements for the Fabrication of Microvascular-like Structures. Acta Biomater. 2017, 66, 272-281. (202) Kou, L.; Huang, T.; Zheng, B.; Han, Y.; Zhao, X.; Gopalsamy, K.; Sun, H.; Gao, C. Coaxial Wet-Spun Yarn Supercapacitors for High-Energy Density and Safe Wearable Electronics. Nat. Commun. 2014, 5, 3754. (203) An, S.; Jo, H. S.; Kim, D. Y.; Lee, H. J.; Ju, B. K.; Al-Deyab, S. S.; Ahn, J. H.; Qin, Y.; Swihart, M. T.; Yarin, A. L.; Yoon, S. S. Self-Junctioned Copper Nanofiber Transparent Flexible Conducting Film via Electrospinning and Electroplating. Adv. Mater. 2016, 28, 71497154.


70

Page 71 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Figure 1 (A) (i) B. mori silkworm silk and (ii) gland with four parts: anterior silk gland (ASG), funnel, middle silk gland (MSG), and posterior silk gland (PSG). Reprinted with permission from ref 24. Copyright 2015 Elsevier. (B) (i) Spider silk web and (ii) a Major ampullated gland divided into four parts: duct, funnel, sac, and tail. Within each gland, there is a pH gradient in different regions. Reprinted with permission from ref 11.


71

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 72 of 84

Figure 2 (A) Schematic description of spider dragline silks’ molecular changes when multiple after pulsed vapor-phase infiltration (MPI) treatment. Reprinted with permission from ref 39. Copyright 2009 American Association for the Advancement of Science. (B) Intrinsically multicolored and luminescent silks generated by feeding silkworms with fluorescent dyes including rhodamine 101, rhodamine 110, and rhodamine B, respectively. Reprinted with permission from ref 41. Copyright 2011 Copyright 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (C) Various morphologies of silk protein-based materials: (i) 3D porous sponge; Reprinted with permission from ref 47. Copyright 2010 Elsevier. (ii) film; Reprinted with permission from ref 51. Copyright 2005 Elsevier. (iii) hydrogel; Reprinted with permission from ref 48. Copyright 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (iv) nanoparticle; Reprinted with permission from ref 52. Copyright 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (v) microcapsule; Reprinted with permission from ref 53. Copyright 2014 Elsevier.


72

Page 73 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

(vi) microneedle patch. Reprinted with permission from ref 54. Copyright 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


73

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 74 of 84

Figure 3 Scheme of different methods for bio-inspired spinning of fibers. (A) Wet spinning; (B) dry spinning; (C) electrospinning; (D) microfluidic spinning; (E) self-assembly; (F) direct writing.


74

Page 75 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Figure 4 (A) (i)A wet spinning set-up, through which recombinant spider spidroins was pumped through a capillary tip into a low-pH collection reservoir; (ii) photo of a single fiber, a wet fiber nest, and fibers on a frame. Reprinted with permission from ref 64. Copyright 2017 Springer Nature. (B) (i-ii) scheme (i)and photograph (ii) of the dry spinning process, by which nematic silk microfibril assembled into regenerated silk fibers; (iii-iv) visual appearance (iii) and polarized light microscopy image (iv) of the fibers. Reprinted with permission from ref 73. Copyright 2017 Springer Nature. (C) (i) Scheme of the multi-channel electrospinning system; (ii) SEM images of fibers with multichannel structures. Reprinted with permission from ref 84. Copyright 2007 American Chemical Society. (D) (i) Scheme of the combined electrospinning/electrospraying approach; (ii) SEM image of fibers with spindle-knotted structure. Reprinted with permission from ref 87. Copyright 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


75

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 76 of 84

Figure 5 Microfluidic spinning of biomimetic fibers. (A) (i-ii) Scheme (i) and (ii) the mask layout of the microfluidic chip combining the laminar flow mixing part and the elongational flow part; (iii) micrograph of fibrous eADF3 assembled in the microfluidic device. Reprinted with permission from ref 103. Copyright 2008 National Academy of Sciences. (B) (i-ii) Scheme (i) and (ii) photograph of a PDMS chip with individually controlled inlets mimicking spider spinning; (iii) detailed illustration of the valve; (iv) scheme and fluorescence image of the twisting fibres. Reprinted with permission from ref 110. Copyright 2011 Springer Nature. (C) Bioinspired fibers with multi-compartmental morphologies. (i) Scheme and photographs of the multi-barrel microfluidic device and the fiber formation process; (ii) cross-sectional CLSM images of the multicompartmental microfibers. Reprinted with permission from ref 111. Copyright 2014 Wiley-VCH


76

Page 77 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Verlag GmbH & Co. KGaA, Weinheim. (D) Bioinspired fibers with helical structures. (from left to right) scheme illustration and CLSM images of fibers with hollow, core-shell, and doublehelical architectures, respectively. Reprinted with permission from ref 101. Copyright 2017 WileyVCH Verlag GmbH & Co. KGaA, Weinheim. (E) Bioinspired fibers with spindle-knotted structures. (i) Scheme of the microfluidic device and the generation mechanism; (ii-iii) optical (ii) and CLSM (iii) images of the resultant fibers. Reprinted with permission from ref 112. Copyright 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (F) Bioinspired bamboo-like microfibers in dehydrated state. Reprinted with permission from ref 114. Copyright 2014 WileyVCH Verlag GmbH & Co. KGaA, Weinheim.


77

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 78 of 84

Figure 6 (A) Direct drawing of fibers through supramolecular assembly. (i) Photograph of the drawing process; (ii-iii) optical (ii) and SEM (iii) images of the fiber after fast dehydration; (iv) cross-sectional SEM image showing silica NPs inside the polymer matrix; (v-vii) SEM images showing internal hierarchical feature with nanoscale fibrils. Reprinted with permission from ref 116. Copyright 2017 National Academy of Sciences. (B) Direct writing of a 3D array of silk fibers.(i) Schematic illustration; (ii-iii) 3D fiber architectures of a square lattice (ii) and a circular web (iii); (iv) a magnified image. Reprinted with permission from ref 123. Copyright 2008 WileyVCH Verlag GmbH & Co. KGaA, Weinheim. (C) Bio-inspired generation of fibers with hierarchical helix structures through a method combining drying spinning with a twisting procedure. (i) Scheme of the helical assembly of MWCNTs into primary and secondary fibers; (ii) the primary fiber; (iii-iv) secondary fibers with twisting angles of appropriately 6o and 43o,


78

Page 79 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

respectively. Reprinted with permission from ref 127. Copyright 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


79

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 80 of 84

Figure 7 Examples of biomimetic fibers for biomedical applications. (A) A nanofibers network incorporated with biological cue in mimic of native articular cartilage ECM. Reprinted with permission from ref 138. Copyright 2012 National Academy of Sciences. (B) Cell-laden hydrogel microfibers with tunable multicompartmental or core-shell structures. Reprinted with permission from ref 151. Copyright 2016 American Chemical Society. (C) A helical microfiber attached with cell-seeded film as a mechanical sensor. Reprinted with permission from ref 101. Copyright 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (D) A stretchable microfiber strain sensor with beads-on-a-string structure: (i) the uneven surface strain distribution; (ii) the integrated device adhered onto lower limb joint for sports monitoring. Reprinted with permission from ref 170. Copyright 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


80

Page 81 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Figure 8 Examples of biomimetic fibers in wettability manipulations. (A) Microfiber with periodic spindle-shaped cavity knots and joints for water capture: (i-ii) SEM images showing (i) different nanostructures in the knots and joints surface and (ii) the cavity structure of the knots; (iii) the fiber network for water collection. Reprinted with permission from ref 179. Copyright 2017 Springer Nature. (B) An aligned nanofiber network for unidirectional water transportation: (i) SEM image of the aligned fibrous structure; (ii) drop spreading was facilitated in parallel with the fiber orientation while hindered in perpendicular direction; (iii) a nanofibrous surface created with a wetting gradient; (iv) time-sequent photographs showing microchemical reaction process. Reprinted with permission from ref 182. Copyright 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (C) Nanofibers film for liquid separation: (i) SEM image showing the porous structured fibrous film. The magnified image in the inset showed nanopores morphology on the fiber surface.


81

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 82 of 84

Reprinted with permission from ref 187. Copyright 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (D) A microfiber based SLIPS coating for liquid repellent usages: (i) bacteria incubated on non-slippery surface (left), silicone oil infused SLIPS surface (middle), and perfluoropolyether infused SLIPS surface (right); (ii) when the surfaces were tilted, bacteria remained pinned on the non-slippery surface (left) while slid down on the SLIPS surfaces (middle and right); (iii-iv) SEM images showing blood cell adhesion on (iii) non-slippery and (iv) SLIPS surface. Reprinted with permission from ref 129. Copyright 2016 American Chemical Society.


82

Page 83 of 84 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Nano

Figure 9 Examples of biomimetic fibers in energy converting applications. (A) A triboelectric energy harvesting device based on frictional contact between an electrospun silk fibroin film and a PI film. Reprinted with permission from ref 194. Copyright 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (B) A micromotor based on short helical microfibers. (i) Time-lapse images showing self-propelled motion of micromotor driven by catalytic decomposition of hydrogen peroxide. (ii-iii) Time-lapse images showing magnetically-mediated (ii) clockwise rotation and (iii) corkscrew motion of the micromotor. Reprinted with permission from ref 199. Copyright 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


83

ACS Nano 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 84 of 84

TOC graphic Spinning and applications of bioinspired fiber systems

Spinning and applications of bioinspired fiber systems: Natural fiber systems provide inspirations for artificial fiber spinning and applications. Recently, natural fibers structures and their formation mechanisms are better understood, and some of the essential factors are implemented in artificial spinning methods, benefiting from advanced manufacturing technologies. The bioinspired artificial fiber materials find an increasingly wide range of biomedical, optoelectronics, and environmental engineering applications.


84

Spinning and Applications of Bioinspired Fiber Systems - ACS Nano

Recommend Documents