Recent Advances in Shape Memory Soft Materials for Biomedical

Review www.acsami.org

Recent Advances in Shape Memory Soft Materials for Biomedical Applications Benjamin Qi Yu Chan,†,‡ Zhi Wei Kenny Low,†,‡ Sylvester Jun Wen Heng,†,‡ Siew Yin Chan,†,§ Cally Owh,† and Xian Jun Loh*,†,‡,∥ †

Institute of Materials Research and Engineering (IMRE), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Singapore Department of Materials Science and Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore § School of Science, Monash University Malaysia, Bandar Sunway, 47500 Selangor Darul Ehsan, Malaysia ∥ Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore 168751, Singapore

Downloaded via UNIV OF CALIFORNIA SANTA BARBARA on July 13, 2018 at 10:36:26 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

‡

ABSTRACT: Shape memory polymers (SMPs) are smart and adaptive materials able to recover their shape through an external stimulus. This functionality, combined with the good biocompatibility of polymers, has garnered much interest for biomedical applications. In this review, we discuss the design considerations critical to the successful integration of SMPs for use in vivo. We also highlight recent work on three classes of SMPs: shape memory polymers and blends, shape memory polymer composites, and shape memory hydrogels. These developments open the possibility of incorporating SMPs into device design, which can lead to vast technological improvements in the biomedical field. KEYWORDS: smart materials, stimuli-responsive materials, shape memory polymers, shape memory polymer blends, shape memory polymer composites, shape memory hydrogels, biomedical applications when exposed to an external stimulus,2−4 such as temperature,5−8 light,9−11 magnetic fields,12−15 and electrical currents,16−19 etc. SMPs are not confined to pure polymeric systems but also polymer blends20,21 and composites (SMPCs)22,23 and polymer networks such as hydrogels.24−26 Shape memory soft materials are lightweight, cheap, and capable of larger recoverable strains than shape memory alloys. These properties make SMPs suitable for actuators,27 sensors,28 microfluidic systems,29 and biomedical applications30 such as vascular grafts and cardiovascular stents,31−33 as well as applications in aerospace technology,34−36 textiles,37 and consumer care products.38 The idea of shape memory effect in polymers has been applied in commercial products as early as the 1960s in the form of heatshrinkable polyethylene tubes used as wire wraps for the purpose of electrical insulation.39 Over the past 3 decades, reports of SMPs activated by different stimuli and exhibiting a variety of

1. INTRODUCTION Stimuli-responsive systems can be found in a myriad of examples in nature. The Mimosa pudica displays thigmonastic responses in which the compound leaves of the plant fold up when touched. Another example is the Dionaea muscipula, or Venus flytrap, which has a leaf-shutting mechanism triggered when hairs on the leaf surface are touched by insects in rapid succession1 (Figure 1I). Such examples provide inspiration for the design of synthetic smart materials (Figure 1II) in which the stimuli-responsiveness of these materials may be used favorably in various applications. Within the wide range of stimuli-responsive materials, much focus has been placed on the study and synthesis of soft stimuliresponsive polymeric materials due to their versatility, enhanced biocompatibility, and potential biodegradability as compared to other classes of materials such as metals and ceramics. In particular, stimuli-responsive polymers such as shape memory polymers (SMPs) utilizing varying stimuli for potential medical applications have been of widespread interest in recent years. SMPs are smart, adaptive soft materials with the ability to recover either permanent or programmed temporary shapes © 2016 American Chemical Society

Received: January 31, 2016 Accepted: March 28, 2016 Published: March 28, 2016 10070

DOI: 10.1021/acsami.6b01295 ACS Appl. Mater. Interfaces 2016, 8, 10070−10087

Review

ACS Applied Materials & Interfaces

evaluation of the biocompatibility. Cell viability assays such as MTT and MTS assays45 are based on the reduction of tetrazolium compound into a colored, insoluble formazan product and are commonly used tests. In addition, cell membrane integrity evaluation by means of lactate dehydrogenase (LDH) assays46 and trypan blue tests47,48 are also well established protocols. These cell membrane integrity assays work on the principle that cytotoxic compounds compromise and rupture cell membranes. This allows cell dyes such as trypan blue to stain dead cells for an observable evaluation of cell viability by cell counting using a hemocytometer. LDH assay, on the other hand, works on the principle that lactate dehydrogenase (LDH) enzymes which are present within living cells are released upon rupture of living cell membranes. LDH reduces pyruvate to lactate and causes a coupling oxidation reaction of reduced nicotinamide adenine dinucleotide (NADH) to the oxidized NAD+ form (Figure 2). NAD+ has a much lower absorbance of 340 nm radiation as compared to NADH, allowing the presence of LDH (and thus cell viability) to be quantifiable by a spectrophotometer. Apart from general biocompatibility, SMPs designed for tissue and blood-facing applications must further consider hemocompatibility issues. 49 For example, a self-expanding SMP endovascular stent must be evaluated for its propensity to cause thrombotic occlusions. With this consideration in mind, care must be taken in the selection of components when designing the SMP, such as selection of blood-inert components or oligomers for the synthesis of SMPs to be used in blood-facing applications. Govindarajan et al. also proposed that since the shape memory effect in SMPs is not a surface property, it is possible to perform surface modification techniques such as surface roughening, patterning, chemical modification (PVD, CVD, and self-assembled monolayers), and thin coatings to decrease the chance of thrombotic events.50 2.2. Mechanical Properties. In the biomedical context, shape memory polymers, which possess an extensive range of mechanical and physical properties, allow for the better catering of adaptive materials to the requirements of human tissue. In particular, shape memory polymers have shown great potential in matching the physical properties of soft biological tissue, allowing for the expansion of the biomedical applicability of smart materials to beyond the previously explored aspects of hard biological tissue, an area well served by shape memory alloys.51 The matching of the physical properties of biomedical materials to those of biological tissue is particularly crucial in the design of prototypes with the intended purpose of replacing or augmenting natural tissue function. Natural biological tissue is subjected to a variety of physiological conditions within the body that include, but are not limited to, compressive stresses during

Figure 1. (I) Leaf-shutting mechanism of the Venus flytrapan example of a stimuli-responsive system found in natureand (II) illustration of the shape memory effect in synthetic SMPs inspired by nature. Adapted by permission from Macmillan Publishers Ltd.: Nature1, copyright 2005.

features have been increasingly published. Therefore, there is a need for a categorical review highlighting the recent advances in this area. This work aims to present a brief review on the considerations in designing a SMP suitable for biomedical applications, as well as recent reports of soft polymeric materials exhibiting shape memory effectin particular SMPs blends, SMP composites (SMPCs), and shape memory hydrogelsand their use in biomedical applications, particularly in the past 3 years. For further details on the working mechanism of the shape memory effect in polymeric soft materials not covered herein, readers are referred to comprehensive reviews previously published.40−44

2. DESIGN CONSIDERATIONS OF SMPS FOR BIOMEDICAL APPLICATIONS SMPs offer interesting combinations of functionalities and tunable properties and have thus emerged as an increasingly attractive proposition for biomedical applications. As such, it is important to consider design requirements of SMPs with regard to their potential utilization as biomedical devices. A brief overview on design considerations such as biocompatibility, mechanical properties matching, biodegradability, and sterilizability will be covered in this section. 2.1. Biocompatibility. One of the most important design considerations of any material for potential biomedical applications is biocompatibility, which is the ability of the material to perform in vivo with an appropriate host response. SMPs designed for biomedical applications in mind are thus expected to be non-cytotoxic as a basic requirement. In vitro cytotoxicity studies by means of cell viability assays and cell membrane integrity assays are widely used tests as initial

Figure 2. Redox reaction of pyruvate and NADH to lactate and NAD+ due to the presence of lactate dehydrogenase (LDH) enzymes. 10071


Review

ACS Applied Materials & Interfaces Table 1. Summary of Shape Memory Polymers Triggered by Various Stimuli refs stimulus

homo-/copolymers

blends

composites

gels

temperature electrical currents magnetic field light water pH ionic concentration

63, 64, 65, 66, 67, 68, 70, 71, 72, 73, 74

20, 75, 76, 77, 78, 79

80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93 100, 101, 102, 103, 104, 105 106, 107, 108, 109 22, 110 86, 111, 112, 113, 114

26, 94, 95, 96, 97, 98, 99

others

124 (microwave)

115, 116, 117 24, 118 119, 120, 121, 122, 123 25 (UV) 125 (redox-reactions) 126 (ultrasound)

rates could be tuned through the variation in their compositions.59 2.4. Sterilizability. As sterilization before clinical use is compulsory for all medical devices, the sterilizability of shape memory polymers developed for biomedical uses must be considered. Sterilization of the SMP must be conducted without compromising its quality. In this regard, the mode of shape memory effect activation must be considered along with conventional considerations such as thermal and chemical stability. Methods of sterilization listed by the U.S. Food and Drug Administration (FDA) guide include exposure to ethylene oxide (EtO) and irradiation, as well as exposure to steam.60 Each of the processes have their advantages and disadvantages that render it difficult for them to cater to all shape memory polymers. The conventional method of steam sterilization, while simple, makes use of a high-temperature range and cannot be applied on thermal shape memory polymers due to its potential to alter their morphological structures.60,61 However, “cold” sterilization techniques developed to circumvent this not only still operate at relatively high temperatures of 30−60 °C61 but also are still plagued by a myriad of issues. For example, lower-temperature irradiation-type sterilization techniques are unsuitable for biodegradable polymers, which are highly prone to deterioration through chain scission, which can be induced by irradiation. Another technique that makes use of low-temperature plasma has resulted in surface modification through plasma etching62 and cytotoxic effects61 in some studies, and even ethylene oxide sterilization, which is currently considered the gold standard, cannot be applied on some water-activated shape memory polymers due to the high-humidity levels involved during the sterilization process.60 Given the limitations of the currently available sterilization methods, it is crucial to consider in the design and development of shape memory polymers their potential to be appropriately sterilized for clinical use.

weight loading, tension during the pumping of the heart, and shear stresses from the movement of blood. It is thus imperative that the shape memory polymers employed have properties that are capable of coping with such forces involved without the loss of function. For example, stiffness and strength are required of the materials used in the production of scaffolds for bone tissue engineering as the scaffold will have to temporarily take on the function of natural bone tissue.52 The consideration of other properties, such as rigidity or flexibility, to minimize damage caused to the surrounding tissue is also important. At the same time, these materials have to possess the optimal characteristics that allow for them to serve their intended functions. The catheter is one example of a biomedical device that requires a balance between these two qualities. Stiff catheters are desired due to the ease of manipulation outside the human body. However, soft catheters will ensure easier manoeuvring within the body and, given the smaller disparity between their rigidity and that of the arterial walls, cause fewer arterial injuries.53 Given the wide range of mechanical properties desired in the various biomedical applications, it is conceivable that shape memory polymers, which possess highly tunable and versatile properties, can find a place of prominence in this arena. 2.3. Biodegradability. Although biodegradation has been associated with a wide range of definitions that depend on the field in question, it has been used in the biomedical field to describe degradation processes through hydrolytic and oxidation reactions.54 Biodegradability is an important consideration in the design of a shape memory polymer that is highly dependent on the intended permanence of the final product. Materials used in permanent biomedical products have to be non-biodegradable in order to resist degradation by the body and ensure that an extended period of functional use can be achieved. On the other hand, for products that are only required to serve a temporary function, the property of biodegradability will allow for a transient existence that eliminates the need for surgical removal after their functional term. Apart from the general property of biodegradability itself, the rate at which biodegradation will occur should also be tailored to best serve the purpose of the product. The field of tissue engineering, for example, sees great potential in materials with controllable degradation rates in scaffold construction as this could allow for the synchronization between scaffold degradation and natural tissue growth and replacement.55 Adjusting the rate of biodegradation can also confer greater control in other shape memory polymer applications such as in drug delivery systems.56−58 Shape memory polymers with adjustable biodegradation qualities have been devised, where their degradation

3. SMPS FOR BIOMEDICAL APPLICATIONS Shape memory homopolymers and copolymers that are most commonly reported are triggered by thermal stimuli. Thermoresponsive SMPs utilize the inherent thermal transitions of the SMP (or its components) to achieve the shape memory effect. Such thermal transitions are either melting (Tm) or glass transition (Tg) temperatures. As the melting transition occurs over a much smaller temperature range as compared to a glass transition, Tm is favored more as a shape transition temperature. A typical programming cycle involves the introduction of strain at or above the thermal transition, followed by cooling to below 10072


Review

ACS Applied Materials & Interfaces the thermal transition to “lock” the SMP in the programmed deformed shape. This temporary shape is maintained due to the restriction of molecular chain motion by either the formation of crystalline domains (with a Tm transition) or a sudden drop in free volume (with a Tg transition). Subsequent exposure to a thermal stimulus above the transition temperature increases chain mobility and triggers the entropy elasticity-driven shape recovery process. Many other types of stimulus can also be used to induce the shape recovery process by incorporating nanoparticles or reinforcements to form SMP composites to improve thermal conductivity or provide heat in the form of inductive or resistive heating as well as photothermal effects. Shape memory behavior in hydrogels, on the other hand, tends to involve the breaking and forming of physical netpoints when triggered by various stimuli. Both SMP composites and SMP hydrogels will be covered in later subsections of this section. A list of SMPs covered in this review is categorized by stimulus type and summarized in Table 1. The SMPs are further categorized into various biomedical applications and summarized in Table 2.

the Alamar blue assay on osteoblast cells.64 In a similar but more recent work, Zhou’s group reported a star-shaped polyurethane synthesized with multiple-arm PCL coupled with MDI and chain extended using 1,4-butylene glycol (BDO). The polyurethane copolymer synthesized with six-arm PCL displayed an impressive triple-shape memory.65 In vitro cytotoxicity tests using the Alamar blue assay showed excellent osteoblast viability. The triple-shape memory polyurethanes reported by Wang et al. and Zhou’s group displayed excellent biocompatibility, making them suitable materials for biomedical applications. Earlier PCLcontaining copolymers reported include work by Yang et al.66 and Garle et al.,67 with proposed applications as stents and treatment of endovascular problems. In general, SMPs can be categorized into two main groups: thermoplastic physically cross-linked systems and chemically cross-linked thermoset networks. Xie et al. recently reported on a chemically cross-linked electroactive SMP comprising six-armed poly(lactic acid) (PLA) and aniline trimer (AT).68 The biodegradable PLA/AT thermoset were proven to be electroactive and displayed excellent mechanical and shape memory properties. Additionally, immunofluorescence, enzyme activity, and relative gene expression tests confirmed the superior osteogenic differentiation capabilities of the copolymer, making it a candidate material for bone tissue engineering applications. Physically cross-linked SMP systems can be processed (and reprocessed) using heat or solvents by overcoming the physical interactions,69 allowing for the SMP to be remolded after synthesis. As such, physically cross-linked SMP systems can be fabricated into many forms to suit various applications. A few of the most notable forms include SMP foams, as well as micro- and nanofibers which bear much potential in biomedical applications. Electrospinning is one processing technique that is of growing popularity due to the increasing interest in nanostructured materials for biomedical applications. Kai et al. explored the many potential applications of electrospun nanofibers, which include tissue engineering,70 drug delivery, and biosensors.128 Chen et al. earlier attempted to produce an electrospun SMP film with reversible fibrous structure using triethoxysilane end-capped poly(urea urethane) copolymer, which is further cross-linked after electrospinning. The group found that the SMP film, which had a stable fibrous structure, showed a faster shape recovery response compared to bulk polymer samples.71 The work serves as a platform to further improve surface and shape memory properties that expands the potential capabilities of SMPs as biomedical materials. Zhang’s laboratory explored the potential of electrospinning nanofibers of a biodegradable shape memory copolymer of D,Llactide copolymerized with trimethylene carbonate.72 The product was a biomimetic scaffold with shape memory effect afforded by the synergistic combination of the properties of nanofibers and SMPs. The scaffold produced displayed excellent shape fixity and recovery and showed good osteoblast proliferation (Figure 3), demonstrating its potential as a scaffold for bone regeneration using minimally invasive medical procedures. Apart from nanofibers, porous SMP structures such as SMP foams may also find potential in biomedical applications. ErndtMarino et al. investigated PCL-diacrylate SMP foams coated with polydopamine (PD) and found that the coated SMP foams promoted the expression of osteogenic proteins of human mesenchymal stem cells (MSCs).73 This indicates PD-coated SMP foams promote human MSC differentiation into

Table 2. Summary of Various Biomedical Applications of Shape Memory Polymers refs applications actuators stents tissue engineering patent ductus arteriosus occlusion device external applications (wound healing) intravascular thrombus removal

homo/ copolymers 32, 66, 67 68, 70, 72, 73 74

blends

composites

27

79 84

gels

121, 122

123 127

3.1. Shape Memory Polymers and Blends. 3.1.1. SMP Homopolymers and Copolymers. SMP homopolymers have been consistently reported and characterized for their properties over the years. Just recently, Collins et al. expanded on the long list of homopolymers displaying shape memory effect in their detailed investigation of the shape memory properties of amorphous thermoplastic poly(p-phenylene) (PPP).63 The study investigated temperature and time effects of the shape programming of PPP on its shape recovery characteristics. However, SMP copolymer systems are of interest, particularly for biomedical applications, due to their versatility brought about by the possibility to mix and match desired properties of different moieties by copolymerization. Linear block copolymer SMP systems make use of phase segregation between hard segments and switching segments with the thermal transition of the switching segments controlling the shape memory effect of the copolymer. In such SMPs, polyurethane and poly(urea urethane) copolymers are the most widely explored in this group, with the urethane and urea functional groups serving as the hard segments due to strong intermolecular interactions, with polymer moieties serving as the switching segment. Polyurea- and polyurethanebased SMPs are highly tailorable and can be synthesized by reacting a wide range of diamine or dihydroxy-terminated oligomers with diisocyanates. Earlier, Wang et al. synthesized a triple-shape memory polyurethane comprising poly(ε-caprolactone) (PCL), methylene diphenyl diisocyanate (MDI), and N,N-bis(2-hydroxyethyl) cinnamamide which displayed good biocompatibility assessed by 10073


Review


Figure 3. (I) SEM micrographs and (II) fluorescence staining images of electrospun poly(D,L-lactide-co-trimethylene carbonate) nanofibers showing good osteoblast attachment and proliferation. Adapted with permission from ref 72. Copyright 2014 American Chemical Society.

osteoblasts. Such foams may find potential applications as selfexpanding scaffolds for bone regeneration. Wierzbicki et al. designed a prototype device using SMP for the occlusion of patent ductus arteriosus,74 a death-threatening congenital deficiency in which the aorta and pulmonary artery of a baby remain connected after birth. The SMP device displayed favorable characteristics such as lower force required for device removal, as well as improved ability of the device to fully expand instead of applying pressure to blood vessel walls (as compared to commercially available devices). 3.1.2. SMP Blends. SMPs are also often blended with other polymers for the purpose of modifying morphology and tuning shape memory behavior. Chatterjee et al. demonstrated that the blending of an ethylene octane copolymer (EOC) with ethylene propylenediene terpolymer (EPDM) displayed superior physical and mechanical behavior due to the compatibility brought about by structural similarities between the blend components.20 The authors also reported significant increase in shape recovery ratio with increasing EPDM content. It was noted however that the shape recovery of the thermoresponsive blend was highly dependent on the heating method, with the blends displaying a distinctly lower recovery ratio when heated by air convection (Figure 4). Zhang et al. recently reported on the blending of poly(Llactide) (PLLA) with poly(ethylene vinyl acetate) (PEVA),

Figure 4. Shape recovery ratio of EOC:EPDM blends heated by hot water (pink) and hot air (yellow). Reprinted from ref 20, Copyright 2015, with permission from Elsevier.

which was previously investigated for its shape memory effect.129 They found that the blending of PLLA into PEVA enhanced the shape fixity and reduced the temperature dependence of fixity on the fixing temperature, as well as increased the shape recovery ratio of the polymer blend above a critical temperature.75 The incorporation of PLLA in the polymer blend may also serve to improve the biocompatibility and biodegradability of the SMP blend for potential biomedical applications. 10074


Review


Figure 5. (I) Shape fixity ratio of various compositions of PLA:ENR blends as compared to that of pure PLA. (II) Shape recovery ratio of various compositions of PLA:ENR blends as compared to that of pure PLA. Reprinted with permission from ref 77. Copyright 2015 American Chemical Society.

Figure 6. “Switch-spring” model of a SMP blend comprising poly(ε-caprolactone) (PCL) and poly(tetramethylene ether) glycol (PTMEG). Reproduced from ref 79 with permission of The Royal Society of Chemistry.

Chen and his colleagues recently reported their findings on biobased SMP based on poly(lactic acid) (PLA) blended with natural rubber (NR)76 and epoxidized natural rubber (ENR)77 followed by vulcanization to obtain blend networks. These blends displayed continuous rubber networks embedded within the PLA phase instead of phase segregated rubber particles in other rubber blend systems. The group found that their blends presented much more superior shape recovery ratios as compared to the PLA homopolymer (Figure 5), made possible by the continuous rubber phase providing a strong driving force for shape recovery. The use of biodegradable PLA resin obtained from renewable sources also makes the PLA:NR and PLA:ENR blends interesting potential options for biomedical materials. Kang et al. developed a two-way SMP blend by building a core and shell composite from an SMP and an elastomer, respectively. The SMP used was synthesized from MDI, PCL, and 1,4butanediol (BD) in varying ratios, while the elastomer used was poly(styrene−butadiene−styrene) (SBS). It was reported to have achieved reversible strains of about 10%.78 Using an alternative method, Wu et al. synthesized another two-way SMP blend with a “switch-spring” composition by introducing an elastomer network to replace the external tension required in the previously mentioned approach. He developed an interpenetrating network (IPN) of crystalline PCL and elastomeric poly(tetramethylene ether) glycol (PTMEG). The crystalline PCL network was first cross-linked on exposure to ultraviolet (UV) light (Figure 6a1) and then stretched and fixed in a strained state (Figure 6a2). Following this, the elastomeric network was then cross-linked with heat and allowed to cool

before releasing the applied stress from the previous step (Figure 6a3). Here, on heating beyond the switching temperature defined by the Tm of PCL crystallites, the crystalline PCL network melts into an amorphous phase and begins to shrink (as it was stretched in the synthesis process), compressing the elastomer network and increasing its stored energy (Figure 6b1). On cooling the material back to room temperature, the stored energy in the elastomeric network is released, helping to orientate the PCL chains during the crystallization process, resulting in an elongated material (Figure 6b2).79 3.2. SMP Composites. Shape memory polymers can often be reinforced with fibrous or particulate fillers to improve their mechanical properties or imbue them with special functions. This is effective in nullifying some of the notable shortcomings of SMPs, for instance, low mechanical strength (e.g., low strength or low Young’s modulus) or problems of uniform stimulation (e.g., inability to heat material uniformly or problems associated with direct heating). The former classifies the use of fillers as reinforcements and can lead to improvements in the strength, stiffness, and recovery force of the SMPs. Carbon and metallic particles, carbon nanotubes (CNTs), carbon nanofibers (CNFs), and glass fibers are but a few notable candidates of such fillers. On the other hand, fillers may also be used to bestow on SMPs alternate ways of triggering shape recovery and multiple-shape memory effects. SMPs may be augmented with electroactive shape memory effect (SME) by introducing conductive fillers such as carbon black or CNTs. Magnetically active SMP composites may be created by introducing magnetic particles 10075


Review


Figure 7. Vapor growth carbon fibers (VGCFs) of different weight fraction dispersed throughout SMP matrix compared to bulk SMP (0.0% VCGF). (I) Association between Young’s modulus and VGCF weight fraction (where, for example, 1.0E+03 represents 1.0 × 103), (II) association between yield stress and VGCF weight fraction, and (III) stress−strain curves (tensile tests) for SMP and SMP with different VCGF weight fraction at temperatures (a) 25, (b) 45, and (c) 65 °C. Reprinted from ref 133, Copyright 2007, with permission from Elsevier.

Figure 8. (I) Electrical conductivity and (II) thermal conductivity of SMPCs with different degrees of CNT dispersion by composition. Reprinted from ref 132, Copyright 2005, with permission from Elsevier.

into the SMP network. It should also be noted that fillers often serve dual purposes, and they can influence the SME of SMPCs in multiple ways. 3.2.1. Reinforcements. 3.2.1.1. Reinforcement with CNTs and Carbon Nanofibers. The introduction of CNTs improves the shape recovery stress,101 compressive performance,130 tensile strength,131 and thermal and electrical conductivity132 of SMP systems. When the CNT-loaded SMPC is deformed, some strain energy is stored in the CNTs, which is released during recovery. The improvement to recovery stress is thus attributed to the degree to which the CNTs deform during programming. Because of their exceptional strength and Young’s modulus, their incorporation into SMPCs contribute to increasing improvements to the Young’s modulus, yield stress, and tensile stress of the SMPCs with increasing loading133 (Figure 7). CNTs are electrically and thermally conductive and hence serve to improve the electrical and thermal conductivities of the SMPCs, with the only difference between the two being the absence of a

percolation threshold for thermal conductivity132 (Figure 8). The dispersion of the CNTs influence their effectiveness in transferring applied loads and are critical to their overall effect on the mechanical properties of the SMPC.132 Current methods employed to incorporate CNTs into the SMP systems include in situ polymerization,134 ultrasonication,135,136 a combination of ultrasonic and three-roll mill mixing,137 chemical functionalization,138 and mechanical melt mixing.101 A recent work by Lu and Huang100 obtained improved behavior of CNT-loaded SMPCs through the synergistic effect of self-assembled carboxylic acid-functionalized CNTs and CNFs. CNT reinforced SMPCs have been around for some time, and recent studies focusing on shape memory polyurethanes (SMPUs) reinforced with CNTs include works by Fonseca et al.,101 Bai et al.,80 Tijing et al.,139 Yu et al.,124 Du et al.,102 and Li et al.130 Such CNT strengthened polyurethanes may find potential applications in small load-bearing biomedical devices such as tracheal and laryngeal stents to provide mechanical support for 10076


Review


properties, excellent shape memory properties, and biocompatibility, as well as faster degradation compared to PPS SMP reported by the group earlier (Figure 10). The BM-embedded SMPC may find potential applications in high-strength transient implants.

the prevention of trachea and larynx collapse. These devices may be collapsed for easy insertion and expanded using the shape memory effect when affixed in the desired location. 3.2.1.2. Reinforcement with Organoclay. The incorporation of small amounts of exfoliated clay into SMPCs can improve mechanical properties140 and shape recovery stress.141 The effect on mechanical properties depends on the balance between the disruption of the soft segments caused by clay incorporation and the content of clay. Organoclay may also be incorporated into SMPCs to act as a filler and physical cross-linker.142 Barwood et al. found that shape memory recovery times were improved significantly with the incorporation of benzyl tallow dimethylammonium-exchanged bentonite (BTDB) into an acrylate-based thermoresponsive SMP81 (Figure 9). Haghayegh

Figure 10. Mass loss of PPS-BM composites of various compositions as compared to pure PPS, indicating a higher degradation rate for the BMembedded SMPC. Reprinted with permission from ref 84. Copyright 2012 American Chemical Society.

Hasan et al. synthesized SMP foams embedded with SiO2 nanoparticles, which reportedly improved the mechanical and thermal properties of the foams. The introduction of these nanoparticles also aided in the SME, showing 77% volume recovery at 0.5% loading of SiO2.85 The group also embedded the SMP foams with Al2O3 and W nanoparticles, reporting higher tensile strength, toughness, and better thermal stability at low levels of loading. At higher concentrations, the nanoparticles tended to form aggregates, interfering with the interactions between polymers, resulting in a reduction in mechanical properties. More recently, Liu et al. presented a thermoresponsive and water-responsive SMPC synthesized by cross-linking cellulose nanocrystals (CNCs) with polycaprolactone (PCL) and poly(ethylene glycol) (PEG) with shape memory transition temperature that was close to human body temperature.86 The presence of CNC improved the mechanical properties of the SMPC. The PCL- and PEG-containing nanocomposite also showed good biocompatibility evaluated by Alamar blue assays on osteoblast cells, indicating its potential as a biomaterial. Typically, SMPs have inadequate physical strength for most applications. With reinforcements to improve their mechanical integrity and recovery stress, it opens up numerous potential applications for SMPs. For instance, these stronger counterparts can be utilized in the making of custom-fitted orthopedic braces or splints. Polymers generally have poor mechanical properties as compared to their metallic and ceramic counterparts.35,133,143−146 With reinforcements to improve their mechanical integrity and recovery stress, it opens up numerous potential applications for SMPs. Another useful aspect of SMPs in general is that, with the SME, they enable minimally invasive surgeries. 3.2.2. Athermal Stimuli-Triggered SMEs. 3.2.2.1. Electroactive SME. The usage of electricity or the passing of a voltage to achieve shape recovery is evidenced in conducting PU

Figure 9. Improved recovery times by incorporating benzyl tallow dimethylammonium exchanged bentonite (BTDB) into poly(tert-butyl acrylate)-co-poly(ethylene glycol) dimethacrylate shape memory nanocomposite. Reprinted from ref 81, Copyright 2014, with permission from Elsevier.

and Sadeghi found that a good dispersion of nanoclay allowed for improved shape memory properties in a polycaprolactone diol (PCL-diol) and 1,4-butanediol (BD) SMPU because of more effective hydrogen bonding between the hydroxyl groups in the modified nanoclay and the hard segments of the SMP network.82 Interesting concepts of shape memory starch−clay bio-nanocomposites with production methods that may be up-scaled have also been conceived.83 3.2.1.3. Reinforcement with Other Particles. Another method to reinforce SMPs involves the introduction of other particles into the network. Some examples include silicon carbide (SiC), silicon dioxide (SiO2), alumina (Al2O3), or tungsten (W) nanoparticles. As with other fillers used as reinforcements, the use of particles that can bond with the polymer chains in the SMP network chemically would promote better SME and improve the mechanical properties of the composite. An added benefit of faster shape memory response can also be had if the embedded particles improve the thermal conductivity of the SMP system. Earlier, Guo et al. reported on a SMP composite made of raw biobased materials comprising poly(propylene sebacate) (PPS) and incorporating boehmite (BM) nanoplatelets as a follow-up to their earlier paper on PPS as a SMP for potential biomedical applications.84 They found that the SMPC transition temperature may be brought close to body temperature by manipulating BM nanoplatelet content and extent of curing. The PPS-BM composites were also found to have improved mechanical 10077


Review


Figure 11. Magnetic field triggered SMP made by the incorporation of surface-modified superparamagnetic nanoparticles. Reprinted with permission from ref 12. Copyright 2006 John Wiley & Sons.

potential biomedical applications. The magnetically active SME mentioned above is triggered due to the heat generated from hysteresis loss when the material is subject to an alternating magnetic field. Zhang et al. incorporated Fe3O4 into nonwoven Nafion nanofibers, and this SMPC exhibited quick and controlled recovery without significant increase of the surface temperature of the material.108 In other recent work by Razzaq et al., the magnetically active SME was achieved by using magnetite nanoparticles in poly(ω-pentadecalactone) networks.109 They reported shape fixity and recovery ratios of up to 95% and 97%, respectively. However, it is noteworthy that the poly(ωpentadecalactone)-magnetite composite reaches high temperatures for actuation, which might limit its use in biomedical applications. Additionally, further biocompatibility studies need to be performed for this composite to provide better evaluation on the suitability of such composites as biomedical devices. As with electroactive SMPCs, magnetically active SMPCs introduce the concept of “remote actuation”. This is particularly useful as magnetic fields are frequently employed in the biomedical field, and magnetic nanoparticles are known to degrade harmlessly in the human body.12 This technology can also be utilized to allow medical professionals to do mechanical adjustments in the patient’s body remotely. It could also be used in remote-activated drug delivery systems. Another potential application is the remote inflation of an intragastric implant to curb a patient’s appetite.151 3.2.2.3. Phototriggered SME. For light actuation, two methods have been investigated. The first of which involves the usage of a laser to heat the polymer,152 causing it to actuate based on the method described earlier for thermoresponsive SMPs. Lu et al. developed a photoactive SMP by incorporating boron nitride and CNT, which reportedly have a synergistic effect, into an epoxy-based SMP.22 The CNTs served to improve the thermal conductivity of the material and its infrared light absorption, while the transferred nitrides aided in the heat transfer to the SMP matrix, resulting in faster shape memory recovery. Shou et al. also developed near-infrared (near-IR) lightresponsive SMPs by incorporating gold nanorods (AuNRs) into a poly(ε-caprolactone) matrix,110 where exposure to near-IR light induced the embedded AuNRs to be heated, triggering the SME. The second method, as reported by Lendlein and colleagues, involves the introduction of cinnamic groups, which can be actuated by ultraviolet light illumination. Here, irradiation with ultraviolet (UV) light greater than a certain specific wavelength causes the formation of cross-links, “fixing” the temporary shape. Upon irradiation with UV light of smaller wavelength, these photosensitive cross-links that were newly formed are cleaved, causing the material to return to its original permanent shape10 (Figure 12). This principle can be applied to other systems containing light-sensitive polymer groups such as azobenzene.153,154

multiwalled carbon nanotube (MWNT) composites, where MWNTs were used to confer electrical conductivity to the SMPs. In this case, the temperature of the sample could be raised locally via Joule heating that occurs through the application of a voltage to trigger the SME, rather than through external heating.147 Other than MWNTs, carbon nanofibers, carbon black (CB), and graphene can also be used for resistive heating to enable electroactive SME.103 As mentioned before, it also has to be noted that the addition of these fillers will also alter the mechanical properties of the SMP system. Furthermore, impregnating the SMP system with conductive particles serves to improve the thermal conductivity of the material and hence reduces recovery times. Of particular interest is the electroactive SMPs based on aniline trimer (AT), as the electroactive segment, and starshaped polylactide synthesized by Xie et al., developed for bone regeneration and bone tissue engineering. It has exceptional biocompatibility, aiding in the osteogenic differentiation of myoblast cells, and it also boasts shape fixity and recovery ratios of up to 100% and 94%, respectively.68 Another example of recent work in electroactive SME is by Mahapatra et al., where the group filled a poly(ε-caprolactone)-based hyperbranched polyurethane with MWNTs. They reported improvements to mechanical properties, shape recovery ratios of above 98%, and fast recovery times.104 Kim et al. also synthesized an electroactive SMP by using thermally reduced graphenes (TRG) as fillers in a SMPU network. They reportedly achieved up to 97% shape recovery ratio.105 3.2.2.2. Magnetic-Field-Triggered SME. Another method of activating shape memory involves the use of magnetic fields. By incorporating surface-modified super-paramagnetic nanoparticles into the SMP matrix, shape actuation can be activated by remote magnetic stimulus (Figure 11). As the SMP composite is subjected to high-frequency magnetic fields, the incorporated nanoparticles transform electromagnetic energy to heat energy via a relaxation process, raising its temperature, resulting in shape recovery.12 This presents a crucial advantage in biomedical applications as magnetic fields can fully penetrate the human body without attenuation. Two vital parameters that might influence the efficiency of magnetically active SME are the size and the volume fraction of the magnetic particles.148 One example of a magnetically active SMPC used iron oxide (Fe3O4) nanoparticle-coated MWNT as fillers in a chemically cross-linked poly(ε-caprolactone) matrix,106 while another simply utilized the ferromagnetic Fe3O4 particles dispersed into an SMPU matrix to achieve the magnetically active SME.107 Fe3O4 particles are found to be suitable for in vivo use and have been widely studied for applications such as magnetic resonance imaging (MRI) contrast agents and hyperthermia procedures for cancer treatment.149,150 In the former work, the electrospun composite fibers by Gong et al. showed good biocompatibility and the cytotoxicity analyses yielded positive results, promising 10078


Review


crystalline structure has to be restored by drying the sample.158 This second method apparently accelerates the shape recovery process, cutting down recovery times significantly. This was demonstrated by Wu et al. in a recent work by incorporating poly(methacrylic acid)-grafted clay into thermoplastic urethane (PMAA-g-clay-TPU), which could achieve shape fixity and recovery ratios of 82% and 91%, respectively.111 Here, water diffuses through the hydrophilic PMAA-g-clay phase, which acts as the switching segment for the SMPC. The fast water absorption and the mechanical adaptiveness of the clay allows for quick water-active SME. In other work, Wu et al. combined poly(glycerol sebacate urethane) (PGSU) with a 23.2 vol % loading of CNCs to obtain an SMPC with shape fixity and recovery ratios of 98% and 99%, respectively.112 In this SMPC, the water-active SME can be attributed to the formation of the continuous CNC network in the polymer matrix. Another work by Wu et al. incorporated hydrophilic poly(vinyl alcohol) (PVA) sub-micrometer particles into a TPU matrix, where a 15 vol % loading of the PVA particles exhibited the best shape memory performance with 97% shape recovery and shape fixity ratios.113 Recently, Liu et al. developed a water-responsive poly(D,Llactide)-microcrystalline cellulose composite.114 This particular SMPC functioned based on water acting as a plasticizer to reduce the Tg of the material, and its good cytocompatibility and biodegradation behavior holds promising applications in the biomedical field. Water-active SMPCs are particularly attractive for use in endovascular applications. Thermal actuation of SMPs entail local heating, which might lead to the damage of nearby tissue.155 This can be effectively avoided by using water-actuated SMPCs, as water is abundant in the bloodstream. 3.2.3. Others. 3.2.3.1. Multiple-Shape Memory Composites. In order for SMPs to exhibit multiple-shape memory effects, the transition temperatures (Ts) of the associated thermal transitions have to be distinct or well separated (Figure 13). This may be achieved by using blends of different polymers, polymerization of multiple polymer network systems, or introduction of fillers with a distinct switching transition. The two most prominent methods of programming tripleSMPCs are two-step programming procedures (2SPP) such as 2SPP-I and 2SPP-II. 2SPP-I involves first heating the tripleSMPC to a temperature that is beyond both thermal transitions (Ts,low and Ts,high), followed by deformation into the first temporary shape A. The SMPC will then be cooled to a

Figure 12. (I) Photoinduced shape memory polymer film and (II) molecular mechanism of photoinduced shape memory effect at various states: (a) permanent shape, (b) spiral temporary shape, and (c) recovered shape by irradiation with UV light. Adapted by permission from Macmillan Publishers Ltd.: Nature10, copyright 2005.

Light-actuated SMPCs can be applied to smart surgical suturing, to avoid directly heating biological tissue. Intravascular laser-activated therapeutic devices have also been developed, as in the application where a thrombus in the brain’s arterial network is mechanically removed.127 3.2.2.4. Water-Triggered SME. Most of what has been mentioned involves actuation via some form of heating, and this is inextricably tied to a local increase in temperature, which might result in varying degrees of thermal tissue damage.155 An interesting way to circumvent this problem would be to use waterwhich is always present in the bloodstream, as a means of triggering this shape recovery effect, after initial discoveries of the effect that water molecules had on lowering Tg.156 By focusing on manipulating Tg, a notable consequence is that actuation can now occur within a larger range of temperatures. In the simplest setup, the water-sensitive SMP would comprise hydrophobic and hydrophilic segments, as the hard and soft segments, respectively. When the water-sensitive SMP is immersed in water, the water molecules penetrate the matrix and interact with the hydrophilic segments, acting as a plasticizer to improve the mobility of the polymer chains of the soft segment.157 This results in the observed fall in Tg, and if the temperature of the surroundings are above this new Tg, actuation can occur. Alternatively, water-sensitive SMPs can also be made by incorporating a hydrophilic or water-swellable component in conjunction with a hydrophobic component. Upon immersion, water molecules will interact with the water-swellable components, causing them to swell, destroying the crystalline structure. In this state, the SMP becomes compliant and can be deformed significantly. To fix the temporary shape, the

Figure 13. Storage modulus changes in a triple-shape SMP with well separated thermal transitions(A) temporary shape (T > Tg,1,Tg,2); (B) intermediate shape (Tg,1 > T > Tg,2); and (C) permanent shape (T < Tg,1, T g,2 )based on dual polymer network by thiol monomers (mercaptoacetate and mercaptopropionate) and vinyls (vinyl sulfone and acrylate). Reprinted with permission from ref 87. Copyright 2014 American Chemical Society. 10079


Review

ACS Applied Materials & Interfaces temperature between Ts,low and Ts,high while maintaining the applied stress. Cooling below Ts,high fixes the temporary shape A by “freezing” the switching domains associated with the higher thermal transition. While maintaining this intermediate temperature, a second temporary shape B can be programmed in a similar manner, where the applied stress is maintained as the polymer is cooled to a lower temperature, Tlow (below both Ts,low and Ts,high). 2SPP-II, on the other hand, involves first heating beyond both Ts,low and Ts,high and fixing the shape by cooling the polymer to Tlow. After which, the polymer is reheated to an intermediate temperature between Ts,low and Ts,high, where shape B is programmed and fixed by maintaining and then cooling the polymer back to Tlow.4 Recently, Chatani et al. synthesized a triple-SMPC from the in situ polymerization of mercaptoacetate (MA), mercaptopropionate (MP), vinyl sulfone, and acrylate. Here, two polymer networks were formed at distinct times, with the MA-vinyl sulfone network forming before the MP-acrylate network.87 These networks had different and distinct Tss, which was vital for triple-SME to be possible. Dong et al. also synthesized a tripleSMPC from a common CNT/epoxy nanocomposite by utilizing self-made epoxy-graf t-polyoxyethylene octyl phenyl ether (EP-gTX100) as an emulsifier.88 The EP-g-TX100 network served as the second reversible phase in this new SMPC system, enabling the triple-SME. In 2014, Nejad et al. synthesized a triple-SMPC foam by curing a mixture of PCL and a composite derived from diglycidyl ether of bisphenol A (DGEBA) and neopentyl glycol diglycidyl ether monomers with poly(propylene glycol) bis(2aminopropyl ether) (Jeffamine D230) added as a cross-linker.89 This mixture eventually separated into PCL-rich and epoxy-rich phases, granting the system triple-SME. The development of multiple-shape memory polymer (MSMP) composites opens the possibility of multiple-shape transitions for biomedical applications. This might allow for more precise actuation and adjustment of complex shapes and their transitions.4 3.2.3.2. Self-Healing SMPCs. The shape memory effect in SMPs can be utilized to aid in the self-healing or self-regeneration of SMP materials in a process termed as shape memory assisted self-healing (SMASH),90,91 or close-then-heal (CTH) selfhealing.92,93,159 These describe the same process, which generally begins with shape memory actuation to first close a crack, following which some components of the SMP system are melted to rebond the crack (Figure 14). Nejad et al. demonstrated this self-healing effect by creating an interwoven polymeric network of PCL and poly(vinyl acetate) (PVA) by dual electrospinning. These systems not only

possessed self-healing capabilities but also exhibited both dualand triple-SME (in dry and wet states, respectively).90 Earlier on, Luo and Mather also developed a shape memory assisted selfhealing coating based on a similar principle, where they distributed PCL fibers randomly within a shape memory epoxy matrix.91 Li and Zhang also constructed an SMPC from strain hardened polyurethane fibres (synthesized from poly(butylene adipate), 4′4-diphenylmethane diisocyanate, and 1,4-butanediol) coated with acrylic conformal coating followed by epoxy coating. The coating improved the shape fixity of the SMP system, and the material showed good healing properties, which were repeatable.92 In an earlier work, Nji and Li synthesized an SMPC by dispersing small amounts of copolyester in a Verif lex polystyrene SMP matrix.93 Here, the shape recovery of the SMP is utilized to close the cracks, following which healing is achieved by the molten thermoplastic particles, as described in the CTH scheme. In their earlier work, they reported healing efficiencies of up to 65% with 6 vol % loading of copolyester in a PS SMP matrix.159 With self-healing SMPCs, we may lengthen the lifespan of surgical implants by repairing them with exposure to stimuli, rather than replacing them constantly. This may be useful in applications where SMPs are used as parts of implanted biomedical devices, or bioactuators. 3.2.3.3. Two-Way Shape Memory Polymer Composites. The guiding principle for two-way shape memory (2W-SM) is the constant stress applied by an external structure or an interpenetrating polymer network onto the SMP component in the composite. The SMPs/SMP fibers are typically deformed at a temperature beyond Ts and allowed to cool at constant strain before an overlying material is set or cured. This second component of the SMPC exerts a constant strain on the SMP to fix the composite in its primary shape. Upon heating beyond Ts, the SMPC can contract to a new secondary shape, and upon cooling, it will once again return to its primary shape (Figure 15).

Figure 15. Two-way shape memory mechanism. Adapted with permission from ref 78. Copyright 2012 IOP Publishing.

A suggested application of 2W-SMPCs in the biomedical field is their usage as artificial tendons or muscles.79 Also, should the constituents of the SMPC be non-biodegradable, retrieval surgery might have to be carried out. In this case, the ability for the SMPC to be reshrunk to its original smaller dimensions (prior to implantation) might be useful. 3.3. Shape Memory Hydrogels. Hydrogels are hydrophilic polymer networks with high water content and good biocompatibility.160 Their soft and wet nature make them very similar to human tissue,161 and they are thus suitable candidates for biomedical applications such as drug delivery,162 tissue engineering,163 and artificial skin.164 However, high water content levels negatively affect the mechanical properties of hydrogels, making them weak and brittle.165,166 This can hinder the ability of shape memory in hydrogels as a minimum level of mechanical robustness is usually required in order to withstand physical deformation during the shape change process.

Figure 14. Self-healing exhibited in an SMPC produced by electrospinning poly(vinyl acetate) (PVAc) and poly(ε-caprolactone) (PCL). (I) Sample damaged by notching with a blade and bending to propagate crack. (II) Sample after allowing it to heal at 75 °C for 10 min. Reprinted with permission from ref 90. Copyright 2015 Cambridge University Press. 10080


Review


Figure 16. (I) Shape memory hydrogel of length 26.3 mm being stretched to a length of 45.2 mm, 170% of its original length, for its temporary shape. The kinetics of shape transitions of shape memory hydrogels can range from (II) seconds to (III) hours. Image I adapted with permission from ref 95. Copyright 2013 American Chemical Society. Image II adapted with permission from ref 26. Copyright 2015 American Chemical Society. Image III reproduced from ref 120 with permission of The Royal Society of Chemistry.

the network to crystallize and hold the gel network in its deformed state, and the authors report a shape fixity value of close to 100%. The permanent shape is then recovered by placing the gel back into water, which causes the dissolution of the PEG crystallites and thus recovery of the strain in the material.115 3.3.2. SME Triggered in Aqueous Environments. Most other stimuli take place within an aqueous environment, in the presence of specific changes in the environment, such as solution pH. Such systems can be potentially useful for biomedical applications if they are designed to be responsive toward physiological conditions. Thermally responsive hydrogels result from the thermal sensitivity of physical cross-linking. The temporary shapes are usually programmed by placing the hydrogels in a heated environment to cause the dissociation of weaker physical crosslinks. This causes the material to soften, and a deformation is then applied. A cooling process follows after, which re-forms the previously broken physical interactions and holds the deformation in place. Yasin et al. reported a hydrogel system which forms physical interactions through a α-cyclodextrin (α-CD) inclusion complex. Cyclodextrin inclusion complexes have been previously shown to be able to form temperature-sensitive aggregates which result in supramolecular hydrogels.171−173 In this system, the hydrogel is held together by covalent cross-linkers, and reinforced with the α-CD inclusion complexes, which gives rise to the thermally responsive shape memory behavior.96 The shape recovery for temperature-sensitive systems tends to take place in less than 1 min. However, the shape recovery temperatures are still slightly high and take place between 60 and 90 °C,26,95−97 and this shows an opportunity for the development of shape memory hydrogels with stimulus temperatures close to the human body temperature of 37 °C. Other athermal stimuli such as pH or ion concentration sensitivities result in interesting shape memory behavior within hydrogels. Hu et al. shared their findings on a DNAfunctionalized hydrogel which shows pH responsiveness through pH-induced Hoogsteen-type interactions. The gel exists as a solid in its permanent shape at pH 7, but softens into a quasiliquid state at either pH 5 or 7, depending on the type of chain functionalized onto the gel.170 Such a system can be potentially useful in parts of the body such as the digestive system where environmental changes in pH are observed. For ion-triggered shape memory behavior, Liu’s group has developed a Zn2+responsive triple shape memory hydrogel, where different cationic concentrations can have either a strengthening or weakening of cross-linking within the hydrogel network.119 Cell

The mediocre mechanical properties of hydrogels are widely recognized as a barrier to the potential use of hydrogels for many applications, and extensive work has been done to improve hydrogel mechanical properties.165−168 Tough hydrogels have been designed, which show remarkable improvements in their tensile strengths (2−8 MPa) while retaining high levels of elongation of up to 700%.94,115,169 Shape memory behavior and mechanical properties in hydrogels are also closely related due to their dependence on the type and degree of cross-linking within the hydrogel network. Similar to blends and composites, shape recoverability and fixity require interchain interactions to be broken and formed easily, while mechanical strength is directly related to the concentration and collective strength of the various forms of cross-links. It is thus important to consider the implications of both features in the design of shape memory hydrogels. The high water content levels in hydrogels enable them to shrink or swell to large degrees through a loss or gain in water, respectively.160,161 This has given rise to shape memory materials capable of undergoing large degrees of deformation between the temporary and permanent states95 (Figure 16I). Water flows in or out of the polymer network via diffusion, and the kinetics of this process are dependent on factors such as network porosity in the various states of deformation. Shape transitions have thus been reported to occur in a wide range from a few seconds26 to several hours120 (Figure 16II,III). This significantly affects the types of applications shape memory hydrogels can be incorporated in. Shape memory response in hydrogels is thus mostly triggered in the presence of water, through either the introduction of water to the system115−117 or a change in the aqueous environment of the material such as temperature,26,95−99 pH,118,170 ion concentration,119−122 or a redox reaction.125 Other types of SME triggers have also been observed in hydrogels, such as UV irradiation25 and ultrasound.126 3.3.1. Water-Triggered SME. Water-triggered shape memory hydrogels hold their temporary shapes through a procedure involving a considerable reduction in water content. The water loss is caused through evaporative loss by taking the gel out of water and can be enhanced by heating the gel.116 As this happens, polymer chains in the network are brought closer and this can result in new interchain interactions, which can hold the strained polymer network in its temporary shape. Cui et al. have designed an extremely strong PEG-based hydrogel with supramolecular cross-links capable of such a water-triggered response. Hydrogel strips are extended and left in air to dry, causing PEG chains in 10081


Review


Figure 17. Micrographs of subcutaneous implanted hydrogels stained by hematoxylin and eosin (H&E). Histological sections of Zn2+-fixed samples (E−H) displayed a faster decrease in inflammatory response as compared to PBS-soaked samples. Reprinted with permission from ref 123. Copyright 2015 American Chemical Society.

materials for use in biomedical applications. However, there are inherent requirements to be met in the design of a SMP system for biomedical use. In order to fulfill the potential of SMPs as biomaterials, design considerations in terms of biocompatibility, mechanical properties, biodegradability, and sterilizability are important factors. Such design considerations and recent advancements in the development of the various classes of SMPs were reported in this review. SMPs are often also blended with other polymers or modified to form composites for the purpose of tuning mechanical properties, morphology, and shape memory behavior. Recent studies also reported multiple-shape SMPs which exhibit various well distinctive thermal transition temperatures, self-healing SMPs utilizing SME, and intermolecular hydrogen bonding to achieve their self-healing properties, as well as two-way SMPs which remember two shapes, viz., one at lower temperature and one at higher temperature. Shape memory hydrogels, on the other hand, have weak mechanical properties that may pose challenges with regard to potential biomedical applications. Concentration of cross-links and the collective strength of various interchain interactions are important factors to be considered in the design shape memory hydrogel systems due to the interdependence between shape memory behavior and mechanical properties. Apart from the types of stimuli mentioned above, shape memory hydrogels can also be triggered by stimuli such as pH, ion concentration, a redox reactions or ultrasound. The research in SMP technology over the past decade has allowed SMPs to find several commercial applications in the biomedical industry. Current applications of SMPs in the biomedical field include stents for the treatment of vascular and laryngeal stenosis. The utilization of SMPs as stents has been claimed to enhance healing after implantation.175 SMPs are also ideal candidate materials for devices to be used in minimally invasive procedures, diagnostic devices, or sensors, tissue scaffolds for cell growth, artificial skin, self-tightening degradable sutures, drug delivery systems, or even as materials for 3D printing of biomedical devices. The development of SMPs may impact the biomedical field and open up new possibilities for designing novel biodevices. Previously, SMP devices suffered from major disadvantage of shape change being one-way and irreversible. With advances in SMP research and technology, two-way/reversible and multipleshape memory systems are now achievable (see section 3.2.3). However, shape change in SMP devices is still either remotely controlled or requires a “user input” to trigger the process. This

viability and other tests have since been conducted on shape memory hydrogels based on this mechanism to investigate their potential use as cell scaffolds.121,122 In another work, Yasin et al. reported a ferric phosphate induced shape memory hydrogel that holds its temporary shape through ionic cross-linking with Fe3+ ions.120 Through the introduction of a reducing agent, erythorbic acid, Fe3+ ions are reduced to Fe2+, which cause the ionic crosslinks to dissociate and result in permanent shape recovery. This system can be potentially applied in the human body and activated through natural means, as the human body contains mechanisms capable of reducing Fe3+ ions to Fe2+ such as the reductase, duodenal cytochrome b.174 In another recent work, Xu et al. showed ion-responsive hydrogels strengthened by hydrogen bonding using a facile onepot synthesis to copolymerize 2-vinyl-4,6-diamino-1,3,5-triazine (VDT), poly(ethylene glycol) diacrylate (PEGDA), and 1vinylimidazole (VI).123 Their study concluded that the inclusion of VI and hydrogen bonding between diaminotriazine (DAT) moieties gave rise to significantly improved mechanical properties. The group further demonstrated that the introduction of zinc ions improved mechanical properties of the hydrogels, and the uptake and release of zinc ions allowed for the hydrogels to display shape memory effect. More importantly, the hydrogels were found to be anti-inflammatory with good wound healing efficacy (Figure 17), making this hydrogel system a potential scaffold material for tissue engineering, particularly in bone tissue engineering applications due to the good mechanical properties displayed.

4. CONCLUSION AND FUTURE PROSPECTS Nature-inspired design of stimuli-responsive materials has led to interesting developments in the field of shape memory soft materials such as shape memory polymers (SMPs), shape memory polymer composites (SMPCs), and shape memory hydrogels. These polymers or hydrogels are able to recover their original state when exposed to specific stimuli such as temperature, electrical currents, magnetic fields, light, and water. Compared to shape memory alloys (SMAs), SMPs have added advantages such as lower raw material cost, lower fabrication and processing costs, tailorable properties, easier shape programming procedures, and low density. Most importantly, SMPs have higher recoverable strains as compared to SMAs which are limited to around 8% deformation, as compared to 800% in SMPs.42 Despite the inherent weakness in mechanical properties of SMPs as compared to SMAs, the advantages that SMPs offer make them attractive propositions as 10082


Review


(5) Lendlein, A.; Langer, R. Biodegradable, Elastic Shape-Memory Polymers for Potential Biomedical Applications. Science 2002, 296 (5573), 1673−1676. (6) Kagami, Y.; Gong, J. P.; Osada, Y. Shape memory behaviors of crosslinked copolymers containing stearyl acrylate. Macromol. Rapid Commun. 1996, 17 (8), 539−543. (7) Kim, B. K.; Lee, S. Y.; Xu, M. Polyurethanes having shape memory effects. Polymer 1996, 37 (26), 5781−5793. (8) Lin, J. R.; Chen, L. W. Study on shape-memory behavior of polyether-based polyurethanes. I. Influence of the hard-segment content. J. Appl. Polym. Sci. 1998, 69 (8), 1563−1574. (9) Iqbal, D.; Samiullah, M. Photo-Responsive Shape-Memory and Shape-Changing Liquid-Crystal Polymer Networks. Materials 2013, 6 (1), 116. (10) Lendlein, A.; Jiang, H.; Junger, O.; Langer, R. Light-induced shape-memory polymers. Nature 2005, 434 (7035), 879−882. (11) Zhang, X.; Zhou, Q.; Liu, H.; Liu, H. UV light induced plasticization and light activated shape memory of spiropyran doped ethylene-vinyl acetate copolymers. Soft Matter 2014, 10 (21), 3748− 3754. (12) Schmidt, A. M. Electromagnetic Activation of Shape Memory Polymer Networks Containing Magnetic Nanoparticles. Macromol. Rapid Commun. 2006, 27 (14), 1168−1172. (13) Zrínyi, M. Intelligent polymer gels controlled by magnetic fields. Colloid Polym. Sci. 2000, 278 (2), 98−103. (14) Szabó, D.; Szeghy, G.; Zrínyi, M. Shape Transition of Magnetic Field Sensitive Polymer Gels. Macromolecules 1998, 31 (19), 6541− 6548. (15) Razzaq, M. Y.; Anhalt, M.; Frormann, L.; Weidenfeller, B. Mechanical spectroscopy of magnetite filled polyurethane shape memory polymers. Mater. Sci. Eng., A 2007, 471 (1−2), 57−62. (16) Sahoo, N. G.; Jung, Y. C.; Cho, J. W. Electroactive Shape Memory Effect of Polyurethane Composites Filled with Carbon Nanotubes and Conducting Polymer. Mater. Manuf. Processes 2007, 22 (4), 419−423. (17) Koerner, H.; Price, G.; Pearce, N. A.; Alexander, M.; Vaia, R. A. Remotely actuated polymer nanocomposites[mdash]stress-recovery of carbon-nanotube-filled thermoplastic elastomers. Nat. Mater. 2004, 3 (2), 115−120. (18) Vaia, R. Nanocomposites: Remote-controlled actuators. Nat. Mater. 2005, 4 (6), 429−430. (19) Luo, X.; Mather, P. T. Conductive shape memory nanocomposites for high speed electrical actuation. Soft Matter 2010, 6 (10), 2146−2149. (20) Chatterjee, T.; Dey, P.; Nando, G. B.; Naskar, K. Thermoresponsive shape memory polymer blends based on alpha olefin and ethylene propylene diene rubber. Polymer 2015, 78, 180−192. (21) Song, J. J.; Kowalski, J.; Naguib, H. E. Synthesis and Characterization of a Bio-Compatible Shape Memory Polymer Blend for Biomedical and Clinical Applications, ASME 2014 Conference on Smart Materials, Adaptive Structures and Intelligent Systems, Paper No. SMASIS2014-7452; American Society of Mechanical Engineers: New York, 2014; p V001T01A008. (22) Lu, H.; Yao, Y.; Huang, W. M.; Leng, J.; Hui, D. Significantly improving infrared light-induced shape recovery behavior of shape memory polymeric nanocomposite via a synergistic effect of carbon nanotube and boron nitride. Composites, Part B 2014, 62, 256−261. (23) Felton, S. M.; Tolley, M. T.; Shin, B.; Onal, C. D.; Demaine, E. D.; Rus, D.; Wood, R. J. Self-folding with shape memory composites. Soft Matter 2013, 9 (32), 7688−7694. (24) Hu, Y.; Lu, C.-H.; Guo, W.; Aleman-Garcia, M. A.; Ren, J.; Willner, I. A Shape Memory Acrylamide/DNA Hydrogel Exhibiting Switchable Dual pH-Responsiveness. Adv. Funct. Mater. 2015, 25, 6867−6874. (25) Feng, W.; Zhou, W.; Zhang, S.; Fan, Y.; Yasin, A.; Yang, H. UVcontrolled shape memory hydrogels triggered by photoacid generator. RSC Adv. 2015, 5 (100), 81784−81789. (26) Li, G.; Zhang, H.; Fortin, D.; Xia, H.; Zhao, Y. Poly(vinyl alcohol)−Poly(ethylene glycol) Double-Network Hydrogel: A General

severely limits the translation of SMP technology into useful, autonomous medical devices. In the future, shape change between multiple programmed shapes could be triggered automatically by dynamic properties (e.g., molecular weight of a transient SMP device or the presence of specific biomarkers) such that a SMP device may potentially function over a longer time period without the need for any form of supervision or manual input. Development of SMP technology in this direction would open opportunities for an even wider range of potential applications such as self-removing biodegradable stents and selfdetaching tissue engineering scaffolds, as well as dynamic drug delivery systems. As such, we foresee that the development of multiple-shape, two-way SMPs with value-added properties such as those mentioned above will become the focus of SMP research in the future. The tailoring of SMP response speeds could be another important direction in SMP research. Current literature provides examples of SMP systems with response times that range between minutes to hours. SMPs with slower response may find value in applications such as medical implants, in order to prevent post-implant shocks caused by sudden alteration of the physiological environment. On the other hand, speed is a key performance indicator for actuators, and fast-response SMPs may thus be of importance in actuating applications such as robotic systems and artificial muscles. More effort can be placed on the design of potential SMP systems with response times and switching temperatures that are tunable after the synthesis and device manufacturing process. Advances in this direction would be greatly advantageous for the SMPs to be used in the biomedical field. Despite the increasing number of reports of SMPs for biomedical applications, smarter material designs with better functionality and performance are imperative to further push boundaries in this area. In summary, SMPs for biomedical applications must be biocompatible, durable, biodegradable, and nonimmunogenic to the human body in order to be applied in the biomedical field. Collaborative research between different branches of science and medicine is required to bring forth further advancements in SMP technology and the translation of research progress from bench to bedside.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS B.Q.Y.C. and Z.W.K.L. acknowledge the A*STAR Graduate Scholarship from A*STAR. S.Y.C. acknowledges funding and support from Monash University Malaysia and IMRE.

■

REFERENCES

(1) Forterre, Y.; Skotheim, J. M.; Dumais, J.; Mahadevan, L. How the Venus flytrap snaps. Nature 2005, 433 (7024), 421−425. (2) Meng, H.; Mohamadian, H.; Stubblefield, M.; Jerro, D.; Ibekwe, S.; Pang, S.-S.; Li, G. Various shape memory effects of stimuli-responsive shape memory polymers. Smart Mater. Struct. 2013, 22 (9), 093001. (3) Lu, H.; Huang, W. M.; Yao, Y. Review of chemo-responsive shape change/memory polymers. Pigm. Resin Technol. 2013, 42 (4), 237−246. (4) Zhao, Q.; Behl, M.; Lendlein, A. Shape-memory polymers with multiple transitions: complex actively moving polymers. Soft Matter 2013, 9 (6), 1744−1755. 10083


Review

ACS Applied Materials & Interfaces Approach to Shape Memory and Self-Healing Functionalities. Langmuir 2015, 31 (42), 11709−11716. (27) Song, J. J.; Chang, H. H.; Naguib, H. E. Biocompatible shape memory polymer actuators with high force capabilities. Eur. Polym. J. 2015, 67, 186−198. (28) Luo, H.; Li, Z.; Yi, G.; Wang, Y.; Zu, X.; Wang, H.; Huang, H.; Liang, Z. Temperature sensing of conductive shape memory polymer composites. Mater. Lett. 2015, 140, 71−74. (29) Balasubramanian, A.; Morhard, R.; Bettinger, C. J. Shape-Memory Microfluidics. Adv. Funct. Mater. 2013, 23 (38), 4832−4839. (30) Serrano, M. C.; Ameer, G. A. Recent Insights Into the Biomedical Applications of Shape-memory Polymers. Macromol. Biosci. 2012, 12 (9), 1156−1171. (31) Wilson, W. M.; Cruden, L. M. Advances in coronary stent technology: Current expectations and new developments. Res. Rep. Clin. Cardiol. 2013, 4, 85−96. (32) Xue, L.; Dai, S.; Li, Z. Biodegradable shape-memory block copolymers for fast self-expandable stents. Biomaterials 2010, 31 (32), 8132−40. (33) Eberhart, R. C.; Su, S.-H.; Nguyen, K. T.; Zilberman, M.; Tang, L.; Nelson, K. D.; Frenkel, P. Review: Bioresorbable polymeric stents: Current status and future promise. J. Biomater. Sci., Polym. Ed. 2003, 14 (4), 299−312. (34) Liu, Y.; Du, H.; Liu, L.; Leng, J. Shape Memory Polymers and Their Composites in Aerospace Applications: A Review. Smart Mater. Struct. 2014, 23, 023001. (35) Lan, X.; Liu, Y.; Lv, H.; Wang, X.; Leng, J.; Du, S. Fiber reinforced shape-memory polymer composite and its application in a deployable hinge. Smart Mater. Struct. 2009, 18 (2), 024002. (36) Campbell, D.; Maji, A. Failure Mechanisms and Deployment Accuracy of Elastic-Memory Composites. Journal of Aerospace Engineering 2006, 19 (3), 184−193. (37) Hu, J.; Meng, H.; Li, G.; Ibekwe, S. A review of stimuli-responsive polymers for smart textile applications. Smart Mater. Struct. 2012, 21 (5), 053001. (38) Lendlein, A.; Kalbfleisch, A.; Duchscherer, A.; Beyer, A.; Graner, S.; Hasson, T. A. A.; Krause, T.; Kratz, K.; Jiang, H. Y.; Moersheim, S., Ghazlan, Y. Method for Hair Treatment with Shape Memory Polymers. US 2007/0275020 A1, 2007. (39) Ota, S. Current status of irradiated heat-shrinkable tubing in Japan. Radiation Physics and Chemistry (1977) 1981, 18 (1−2), 81−87. (40) Lendlein, A.; Kelch, S. Shape-Memory Polymers. Angew. Chem., Int. Ed. 2002, 41 (12), 2034−2057. (41) Mather, P. T.; Luo, X.; Rousseau, I. A. Shape Memory Polymer Research. Annu. Rev. Mater. Res. 2009, 39 (1), 445−471. (42) Liu, C.; Qin, H.; Mather, P. T. Review of progress in shapememory polymers. J. Mater. Chem. 2007, 17 (16), 1543−1558. (43) Ratna, D.; Karger-Kocsis, J. Recent Advances In Shape Memory Polymers And Composites: A Review. J. Mater. Sci. 2008, 43 (1), 254− 269. (44) Wu, X.; Huang, W. M.; Zhao, Y.; Ding, Z.; Tang, C.; Zhang, J. Mechanisms of the Shape Memory Effect in Polymeric Materials. Polymers 2013, 5 (4), 1169−1202. (45) Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983, 65 (1), 55−63. (46) Mitchell, D. B.; Santone, K. S.; Acosta, D. Evaluation of cytotoxicity in cultured cells by enzyme leakage. J. Tissue Cult. Methods 1980, 6 (3−4), 113−116. (47) Tennant, J. R. EVALUATION OF THE TRYPAN BLUE TECHNIQUE FOR DETERMINATION OF CELL VIABILITY. Transplantation 1964, 2 (6), 685−694. (48) Strober, W., Trypan Blue Exclusion Test of Cell Viability. Current Protocols in Immunology; Wiley: New York, 2001; DOI: 10.1002/ 0471142735.ima03bs21. (49) Seyfert, U. T.; Biehl, V.; Schenk, J. In vitro hemocompatibility testing of biomaterials according to the ISO 10993−4. Biomol. Eng. 2002, 19 (2), 91−96.

(50) Govindarajan, T.; Shandas, R. A Survey of Surface Modification Techniques for Next-Generation Shape Memory Polymer Stent Devices. Polymers 2014, 6 (9), 2309−2331. (51) El Feninat, F.; Laroche, G.; Fiset, M.; Mantovani, D. Shape memory materials for biomedical applications. Adv. Eng. Mater. 2002, 4 (3), 91. (52) Hollister, S. J.; Maddox, R.; Taboas, J. M. Optimal design and fabrication of scaffolds to mimic tissue properties and satisfy biological constraints. Biomaterials 2002, 23 (20), 4095−4103. (53) Sokolowski, W.; Metcalfe, A.; Hayashi, S.; Yahia, L. H.; Raymond, J. Medical applications of shape memory polymers. Biomed. Mater. 2007, 2 (1), S23. (54) Calmon-Decriaud, A.; Bellon-Maurel, V.; Silvestre, F. Standard methods for testing the aerobic biodegradation of polymeric materials. Review and perspectives. Blockcopolymers-Polyelectrolytes-Biodegradation; Advances in Polymer Science, Vol. 135; Springer-Verlag: Berlin, 1998; pp 207−226, DOI: 10.1007/3-540-69191-X_3. (55) Sung, H.-J.; Meredith, C.; Johnson, C.; Galis, Z. S. The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis. Biomaterials 2004, 25 (26), 5735−5742. (56) Chen, H.; Li, Y.; Liu, Y.; Gong, T.; Wang, L.; Zhou, S. Highly pHsensitive polyurethane exhibiting shape memory and drug release. Polym. Chem. 2014, 5 (17), 5168−5174. (57) Musiał-Kulik, M.; Kasperczyk, J.; Smola, A.; Dobrzyński, P. Double layer paclitaxel delivery systems based on bioresorbable terpolymer with shape memory properties. Int. J. Pharm. 2014, 465 (1−2), 291−298. (58) Li, G.; Fei, G.; Xia, H.; Han, J.; Zhao, Y. Spatial and temporal control of shape memory polymers and simultaneous drug release using high intensity focused ultrasound. J. Mater. Chem. 2012, 22 (16), 7692− 7696. (59) Kelch, S.; Steuer, S.; Schmidt, A. M.; Lendlein, A. Shape-memory polymer networks from oligo [(ε-hydroxycaproate)-co-glycolate] dimethacrylates and butyl acrylate with adjustable hydrolytic degradation rate. Biomacromolecules 2007, 8 (3), 1018−1027. (60) Wong, Y.; Kong, J.; Widjaja, L. K.; Venkatraman, S. S. Biomedical applications of shape-memory polymers: how practically useful are they? Sci. China: Chem. 2014, 57 (4), 476−489. (61) Yakacki, C.; Lyons, M.; Rech, B.; Gall, K.; Shandas, R. Cytotoxicity and thermomechanical behavior of biomedical shapememory polymer networks post-sterilization. Biomed. Mater. 2008, 3 (1), 015010. (62) Kanjickal, D.; Lopina, S.; Evancho-Chapman, M. M.; Schmidt, S.; Donovan, D. Effects of sterilization on poly(ethylene glycol) hydrogels. J. Biomed. Mater. Res., Part A 2008, 87 (3), 608−617. (63) Collins, D. A.; Yakacki, C. M.; Lightbody, D.; Patel, R. R.; Frick, C. P. Shape-memory behavior of high-strength amorphous thermoplastic poly(para-phenylene). J. Appl. Polym. Sci. 2016, 133 (3), 42903. (64) Wang, L.; Yang, X. F.; Chen, H. M.; Gong, T.; Li, W. B.; Yang, G.; Zhou, S. B. Design of Triple-Shape Memory Polyurethane with Photocrosslinking of Cinnamon Groups. ACS Appl. Mater. Interfaces 2013, 5 (21), 10520−10528. (65) Yang, X.; Wang, L.; Wang, W.; Chen, H.; Yang, G.; Zhou, S. Triple Shape Memory Effect of Star-Shaped Polyurethane. ACS Appl. Mater. Interfaces 2014, 6 (9), 6545−6554. (66) Yang, C.-S.; Wu, H.-C.; Sun, J.-S.; Hsiao, H.-M.; Wang, T.-W. Thermo-Induced Shape-Memory PEG-PCL Copolymer as a DualDrug-Eluting Biodegradable Stent. ACS Appl. Mater. Interfaces 2013, 5 (21), 10985−10994. (67) Garle, A.; Kong, S.; Ojha, U.; Budhlall, B. M. Thermoresponsive Semicrystalline Poly(ε-caprolactone) Networks: Exploiting Crosslinking with Cinnamoyl Moieties to Design Polymers with Tunable Shape Memory. ACS Appl. Mater. Interfaces 2012, 4 (2), 645−657. (68) Xie, M.; Wang, L.; Ge, J.; Guo, B.; Ma, P. X. Strong Electroactive Biodegradable Shape Memory Polymer Networks Based on Star-Shaped Polylactide and Aniline Trimer for Bone Tissue Engineering. ACS Appl. Mater. Interfaces 2015, 7 (12), 6772−6781. (69) Chan, B. Q. Y.; Liow, S. S.; Loh, X. J. RSC Adv. 2016, 6, 34946− 34954. 10084


Review

ACS Applied Materials & Interfaces (70) Kai, D.; Prabhakaran, M. P.; Chan, B. Q. Y.; Liow, S. S.; Ramakrishna, S.; Xu, F.; Loh, X. J. Elastic poly(ε-caprolactone)polydimethylsiloxane copolymer fibers with shape memory effect for bone tissue engineering. Biomed. Mater. 2016, 11 (1), 015007. (71) Chen, H.; Cao, X.; Zhang, J.; Zhang, J.; Ma, Y.; Shi, G.; Ke, Y.; Tong, D.; Jiang, L. Electrospun shape memory film with reversible fibrous structure. J. Mater. Chem. 2012, 22 (42), 22387−22391. (72) Bao, M.; Lou, X.; Zhou, Q.; Dong, W.; Yuan, H.; Zhang, Y. Electrospun Biomimetic Fibrous Scaffold from Shape Memory Polymer of PDLLA-co-TMC for Bone Tissue Engineering. ACS Appl. Mater. Interfaces 2014, 6 (4), 2611−2621. (73) Erndt-Marino, J. D.; Munoz-Pinto, D. J.; Samavedi, S.; JimenezVergara, A. C.; Diaz-Rodriguez, P.; Woodard, L.; Zhang, D.; Grunlan, M. A.; Hahn, M. S. Evaluation of the Osteoinductive Capacity of Polydopamine-Coated Poly(ε-caprolactone) Diacrylate Shape Memory Foams. ACS Biomater. Sci. Eng. 2015, 1 (12), 1220−1230. (74) Wierzbicki, M. A.; Bryant, J.; Miller, M. W.; Keller, B.; Maitland, D. J. Mechanical and in vitro evaluation of an experimental canine patent ductus arteriosus occlusion device. Journal of the Mechanical Behavior of Biomedical Materials 2016, 59, 156−167. (75) Zhang, Z.-x.; Liao, F.; He, Z.-z.; Yang, J.-h.; Huang, T.; Zhang, N.; Wang, Y.; Gao, X.-l. Tunable shape memory behaviors of poly(ethylene vinyl acetate) achieved by adding poly(L-lactide). Smart Mater. Struct. 2015, 24 (12), 125002. (76) Chen, Y.; Yuan, D.; Xu, C. Dynamically Vulcanized Biobased Polylactide/Natural Rubber Blend Material with Continuous CrossLinked Rubber Phase. ACS Appl. Mater. Interfaces 2014, 6 (6), 3811− 3816. (77) Chen, Y.; Chen, K.; Wang, Y.; Xu, C. Biobased Heat-Triggered Shape-Memory Polymers Based on Polylactide/Epoxidized Natural Rubber Blend System Fabricated via Peroxide-Induced Dynamic Vulcanization: Co-continuous Phase Structure, Shape Memory Behavior, and Interfacial Compatibilization. Ind. Eng. Chem. Res. 2015, 54 (35), 8723−8731. (78) Kang, T.-H.; Lee, J.-M.; Yu, W.-R.; Youk, J. H.; Ryu, H. W. Twoway actuation behavior of shape memory polymer/elastomer core/shell composites. Smart Mater. Struct. 2012, 21 (3), 035028. (79) Wu, Y.; Hu, J.; Han, J.; Zhu, Y.; Huang, H.; Li, J.; Tang, B. Twoway shape memory polymer with ″switch-spring″ composition by interpenetrating polymer network. J. Mater. Chem. A 2014, 2 (44), 18816−18822. (80) Bai, Y.; Zhang, Y.; Wang, Q.; Wang, T. Shape memory properties of multi-walled carbon nanotube/polyurethane composites prepared by in situ polymerization. J. Mater. Sci. 2013, 48 (5), 2207−2214. (81) Barwood, M. J.; Breen, C.; Clegg, F.; Hammond, C. L. The effect of organoclay addition on the properties of an acrylate based, thermally activated shape memory polymer. Appl. Clay Sci. 2014, 102, 41−50. (82) Haghayegh, M.; Mir Mohamad Sadeghi, G. Synthesis of shape memory polyurethane/clay nanocomposites and analysis of shape memory, thermal, and mechanical properties. Polym. Compos. 2012, 33 (6), 843−849. (83) Coativy, G.; Gautier, N.; Pontoire, B.; Buléon, A.; Lourdin, D.; Leroy, E. Shape memory starch−clay bionanocomposites. Carbohydr. Polym. 2015, 116, 307−313. (84) Guo, W.; Kang, H.; Chen, Y.; Guo, B.; Zhang, L. Stronger and Faster Degradable Biobased Poly(propylene sebacate) as Shape Memory Polymer by Incorporating Boehmite Nanoplatelets. ACS Appl. Mater. Interfaces 2012, 4 (8), 4006−4014. (85) Hasan, S. M.; Thompson, R. S.; Emery, H.; Nathan, A. L.; Weems, A. C.; Zhou, F.; Monroe, M. B. B.; Maitland, D. J. Modification of shape memory polymer foams using tungsten, aluminum oxide, and silicon dioxide nanoparticles. RSC Adv. 2016, 6 (2), 918−927. (86) Liu, Y.; Li, Y.; Yang, G.; Zheng, X.; Zhou, S. Multi-StimulusResponsive Shape-Memory Polymer Nanocomposite Network CrossLinked by Cellulose Nanocrystals. ACS Appl. Mater. Interfaces 2015, 7 (7), 4118−4126. (87) Chatani, S.; Wang, C.; Podgórski, M.; Bowman, C. N. Triple Shape Memory Materials Incorporating Two Distinct Polymer

Networks Formed by Selective Thiol−Michael Addition Reactions. Macromolecules 2014, 47 (15), 4949−4954. (88) Dong, Y.; Xia, H.; Zhu, Y.; Ni, Q.-Q.; Fu, Y. Effect of epoxy-graftpolyoxyethylene octyl phenyl ether on preparation, mechanical properties and triple-shape memory effect of carbon nanotube/waterborne epoxy nanocomposites. Compos. Sci. Technol. 2015, 120, 17−25. (89) Nejad, H. B.; Baker, R. M.; Mather, P. T. Preparation and characterization of triple shape memory composite foams. Soft Matter 2014, 10 (40), 8066−8074. (90) Birjandi Nejad, H.; Robertson, J. M.; Mather, P. T. Interwoven polymer composites via dual-electrospinning with shape memory and self-healing properties. MRS Commun. 2015, 5 (02), 211−221. (91) Luo, X.; Mather, P. T. Shape Memory Assisted Self-Healing Coating. ACS Macro Lett. 2013, 2 (2), 152−156. (92) Li, G.; Zhang, P. A self-healing particulate composite reinforced with strain hardened short shape memory polymer fibers. Polymer 2013, 54 (18), 5075−5086. (93) Nji, J.; Li, G. Damage healing ability of a shape-memory-polymerbased particulate composite with small thermoplastic contents. Smart Mater. Struct. 2012, 21 (2), 025011. (94) Zhang, Y.; Li, Y.; Liu, W. Dipole−Dipole and H-Bonding Interactions Significantly Enhance the Multifaceted Mechanical Properties of Thermoresponsive Shape Memory Hydrogels. Adv. Funct. Mater. 2015, 25 (3), 471−480. (95) Hao, J.; Weiss, R. A. Mechanically Tough, Thermally Activated Shape Memory Hydrogels. ACS Macro Lett. 2013, 2 (1), 86−89. (96) Yasin, A.; Zhou, W.; Yang, H.; Li, H.; Chen, Y.; Zhang, X. Shape Memory Hydrogel based on a Hydrophobically-Modified Polyacrylamide (HMPAM)/α-CD Mixture via a Host-Guest Approach. Macromol. Rapid Commun. 2015, 36 (9), 845−851. (97) Gulyuz, U.; Okay, O. Self-Healing Poly(acrylic acid) Hydrogels with Shape Memory Behavior of High Mechanical Strength. Macromolecules 2014, 47 (19), 6889−6899. (98) Hasnat Kabir, M.; Hazama, T.; Watanabe, Y.; Gong, J.; Murase, K.; Sunada, T.; Furukawa, H. Smart hydrogel with shape memory for biomedical applications. J. Taiwan Inst. Chem. Eng. 2014, 45 (6), 3134− 3138. (99) Bilici, C.; Okay, O. Shape Memory Hydrogels via Micellar Copolymerization of Acrylic Acid and n-Octadecyl Acrylate in Aqueous Media. Macromolecules 2013, 46 (8), 3125−3131. (100) Lu, H.; Huang, W. M. Synergistic effect of self-assembled carboxylic acid-functionalized carbon nanotubes and carbon fiber for improved electro-activated polymeric shape-memory nanocomposite. Appl. Phys. Lett. 2013, 102 (23), 231910. (101) Fonseca, M. A.; Abreu, B.; Gonçalves, F. A. M. M.; Ferreira, A. G. M.; Moreira, R. A. S.; Oliveira, M. S. A. Shape memory polyurethanes reinforced with carbon nanotubes. Composite Structures 2013, 99, 105− 111. (102) Du, F.-P.; Ye, E.-Z.; Yang, W.; Shen, T.-H.; Tang, C.-Y.; Xie, X.L.; Zhou, X.-P.; Law, W.-C. Electroactive shape memory polymer based on optimized multi-walled carbon nanotubes/polyvinyl alcohol nanocomposites. Composites, Part B 2015, 68, 170−175. (103) Lu, H.; Yao, Y.; Lin, L. Carbon-based reinforcement in shapememory polymer composite for electrical actuation. Pigm. Resin Technol. 2013, 43 (1), 26−34. (104) Mahapatra, S. S.; Yadav, S. K.; Yoo, H. J.; Ramasamy, M. S.; Cho, J. W. Tailored and strong electro-responsive shape memory actuation in carbon nanotube-reinforced hyperbranched polyurethane composites. Sens. Actuators, B 2014, 193, 384−390. (105) Kim, J. T.; Jeong, H. J.; Park, H. C.; Jeong, H. M.; Bae, S. Y.; Kim, B. K. Electroactive shape memory performance of polyurethane/ graphene nanocomposites. React. Funct. Polym. 2015, 88, 1−7. (106) Gong, T.; Li, W.; Chen, H.; Wang, L.; Shao, S.; Zhou, S. Remotely actuated shape memory effect of electrospun composite nanofibers. Acta Biomater. 2012, 8 (3), 1248−1259. (107) Chung, Y.-C.; Choi, J. W.; Choi, M. W.; Chun, B. C. Characterization of Flexibly Linked Shape Memory Polyurethane Composite with Magnetic Property. J. Thermoplast. Compos. Mater. 2012, 25 (3), 283−303. 10085


Review

ACS Applied Materials & Interfaces (108) Zhang, F. H.; Zhang, Z. C.; Luo, C. J.; Lin, I. T.; Liu, Y.; Leng, J.; Smoukov, S. K. Remote, fast actuation of programmable multiple shape memory composites by magnetic fields. J. Mater. Chem. C 2015, 3 (43), 11290−11293. (109) Razzaq, M. Y.; Behl, M.; Nöchel, U.; Lendlein, A. Magnetically controlled shape-memory effects of hybrid nanocomposites from oligo(ω-pentadecalactone) and covalently integrated magnetite nanoparticles. Polymer 2014, 55 (23), 5953−5960. (110) Shou, Q.; Uto, K.; Iwanaga, M.; Ebara, M.; Aoyagi, T. Nearinfrared light-responsive shape-memory poly([epsiv]-caprolactone) films that actuate in physiological temperature range. Polym. J. 2014, 46 (8), 492−498. (111) Wu, T.; O’Kelly, K.; Chen, B. Poly(methacrylic acid)-grafted clay−thermoplastic elastomer composites with water-induced shapememory effects. J. Polym. Sci., Part B: Polym. Phys. 2013, 51 (20), 1513− 1522. (112) Wu, T.; Frydrych, M.; O’Kelly, K.; Chen, B. Poly(glycerol sebacate urethane)−Cellulose Nanocomposites with Water-Active Shape-Memory Effects. Biomacromolecules 2014, 15 (7), 2663−2671. (113) Wu, T.; O’Kelly, K.; Chen, B. Poly(vinyl alcohol) particlereinforced elastomer composites with water-active shape-memory effects. Eur. Polym. J. 2014, 53, 230−237. (114) Liu, Y.; Li, Y.; Chen, H.; Yang, G.; Zheng, X.; Zhou, S. Waterinduced shape-memory poly(d,l-lactide)/microcrystalline cellulose composites. Carbohydr. Polym. 2014, 104, 101−108. (115) Cui, Y.; Tan, M.; Zhu, A.; Guo, M. Mechanically strong and stretchable PEG-based supramolecular hydrogel with water-responsive shape-memory property. J. Mater. Chem. B 2014, 2 (20), 2978−2982. (116) Zhang, J. L.; Huang, W. M.; Gao, G.; Fu, J.; Zhou, Y.; Salvekar, A. V.; Venkatraman, S. S.; Wong, Y. S.; Tay, K. H.; Birch, W. R. Shape memory/change effect in a double network nanocomposite tough hydrogel. Eur. Polym. J. 2014, 58, 41−51. (117) Zhao, T.; Tan, M.; Cui, Y.; Deng, C.; Huang, H.; Guo, M. Reactive macromolecular micelle crosslinked highly elastic hydrogel with water-triggered shape-memory behaviour. Polym. Chem. 2014, 5 (17), 4965−4973. (118) Meng, H.; Zheng, J.; Wen, X.; Cai, Z.; Zhang, J.; Chen, T. pHand Sugar-Induced Shape Memory Hydrogel Based on Reversible Phenylboronic Acid−Diol Ester Bonds. Macromol. Rapid Commun. 2015, 36 (6), 533−537. (119) Han, Y.; Bai, T.; Liu, Y.; Zhai, X.; Liu, W. Zinc Ion Uniquely Induced Triple Shape Memory Effect of Dipole−Dipole Reinforced Ultra-High Strength Hydrogels. Macromol. Rapid Commun. 2012, 33 (3), 225−231. (120) Yasin, A.; Li, H.; Lu, Z.; Rehman, S. u.; Siddiq, M.; Yang, H. A shape memory hydrogel induced by the interactions between metal ions and phosphate. Soft Matter 2014, 10 (7), 972−977. (121) Nan, W.; Wang, W.; Gao, H.; Liu, W. Fabrication of a shape memory hydrogel based on imidazole-zinc ion coordination for potential cell-encapsulating tubular scaffold application. Soft Matter 2013, 9 (1), 132−137. (122) Han, Y.; Bai, T.; Liu, W. Controlled Heterogeneous Stem Cell Differentiation on a Shape Memory Hydrogel Surface. Sci. Rep. 2014, 4, 5815. (123) Xu, B.; Li, Y.; Gao, F.; Zhai, X.; Sun, M.; Lu, W.; Cao, Z.; Liu, W. High Strength Multifunctional Multiwalled Hydrogel Tubes: IonTriggered Shape Memory, Antibacterial, and Anti-inflammatory Efficacies. ACS Appl. Mater. Interfaces 2015, 7 (30), 16865−16872. (124) Yu, K.; Liu, Y.; Leng, J. Shape memory polymer/CNT composites and their microwave induced shape memory behaviors. RSC Adv. 2014, 4 (6), 2961−2968. (125) Miyamae, K.; Nakahata, M.; Takashima, Y.; Harada, A. SelfHealing, Expansion−Contraction, and Shape-Memory Properties of a Preorganized Supramolecular Hydrogel through Host−Guest Interactions. Angew. Chem. 2015, 127 (31), 9112−9115. (126) Li, G.; Yan, Q.; Xia, H.; Zhao, Y. Therapeutic-UltrasoundTriggered Shape Memory of a Melamine-Enhanced Poly(vinyl alcohol) Physical Hydrogel. ACS Appl. Mater. Interfaces 2015, 7 (22), 12067− 12073.

(127) Small, W., IV; Wilson, T. S.; Benett, W. J.; Loge, J. M.; Maitland, D. J. Laser-activated shape memory polymer intravascular thrombectomy device. Opt. Express 2005, 13 (20), 8204−8213. (128) Kai, D.; Liow, S. S.; Loh, X. J. Biodegradable polymers for electrospinning: Towards biomedical applications. Mater. Sci. Eng., C 2014, 45, 659−670. (129) Li, F.; Zhu, W.; Zhang, X.; Zhao, C.; Xu, M. Shape memory effect of ethylene−vinyl acetate copolymers. J. Appl. Polym. Sci. 1999, 71 (7), 1063−1070. (130) Li, H.; Zhong, J.; Meng, J.; Xian, G. The reinforcement efficiency of carbon nanotubes/shape memory polymer nanocomposites. Composites, Part B 2013, 44 (1), 508−516. (131) Raja, M.; Ryu, S. H.; Shanmugharaj, A. M. Thermal, mechanical and electroactive shape memory properties of polyurethane (PU)/poly (lactic acid) (PLA)/CNT nanocomposites. Eur. Polym. J. 2013, 49 (11), 3492−3500. (132) Song, Y. S.; Youn, J. R. Influence of dispersion states of carbon nanotubes on physical properties of epoxy nanocomposites. Carbon 2005, 43 (7), 1378−1385. (133) Ni, Q.-Q.; Zhang, C.-s.; Fu, Y.; Dai, G.; Kimura, T. Shape memory effect and mechanical properties of carbon nanotube/shape memory polymer nanocomposites. Composite Structures 2007, 81 (2), 176−184. (134) Coleman, J. N.; Khan, U.; Gun’ko, Y. K. Mechanical Reinforcement of Polymers Using Carbon Nanotubes. Adv. Mater. 2006, 18 (6), 689−706. (135) Ebara, M.; Kotsuchibashi, Y.; Narain, R.; Idota, N.; Kim, Y. J.; Hoffman, J. M.; Uto, K.; Aoyagi, T. Smart Biomaterials; Springer: Tokyo, Japan, 2014. (136) Ding, B.; Yu, J. Electrospun Nanofibers for Energy and Environmental Applications; Springer: Berlin, Heidelberg, 2014. (137) Li, G., Meng, H., Eds. Recent Advances in Smart Self-Healing Polymers and Composites; Woodhead, Elsevier Science: Cambridge, U.K., 2015. (138) Jung, Y. C.; Sahoo, N. G.; Cho, J. W. Polymeric nanocomposites of polyurethane block copolymers and functionalized multi-walled carbon nanotubes as crosslinkers. Macromol. Rapid Commun. 2006, 27 (2), 126−131. (139) Tijing, L. D.; Park, C.-H.; Choi, W. L.; Ruelo, M. T. G.; Amarjargal, A.; Pant, H. R.; Im, I.-T.; Kim, C. S. Characterization and mechanical performance comparison of multiwalled carbon nanotube/ polyurethane composites fabricated by electrospinning and solution casting. Composites, Part B 2013, 44 (1), 613−619. (140) Pattanayak, A.; Jana, S. C. High-strength and low-stiffness composites of nanoclay-filled thermoplastic polyurethanes. Polym. Eng. Sci. 2005, 45 (11), 1532−1539. (141) Cao, F.; Jana, S. C. Nanoclay-tethered shape memory polyurethane nanocomposites. Polymer 2007, 48 (13), 3790−3800. (142) Kim, M. S.; Jun, J. K.; Jeong, H. M. Shape memory and physical properties of poly(ethyl methacrylate)/Na-MMT nanocomposites prepared by macroazoinitiator intercalated in Na-MMT. Compos. Sci. Technol. 2008, 68 (7−8), 1919−1926. (143) Meng, H.; Li, G. A review of stimuli-responsive shape memory polymer composites. Polymer 2013, 54 (9), 2199−2221. (144) Nair, D. P.; Cramer, N. B.; Scott, T. F.; Bowman, C. N.; Shandas, R. Photopolymerized thiol-ene systems as shape memory polymers. Polymer 2010, 51 (19), 4383−4389. (145) Wang, W.; Ping, P.; Chen, X.; Jing, X. Biodegradable polyurethane based on random copolymer of L-lactide and ϵcaprolactone and its shape-memory property. J. Appl. Polym. Sci. 2007, 104 (6), 4182−4187. (146) Leng, J.; Du, S. Shape-memory polymers and multifunctional composites; CRC Press: Boca Raton, FL, USA, 2010. (147) Cho, J. W.; Kim, J. W.; Jung, Y. C.; Goo, N. S. Electroactive Shape-Memory Polyurethane Composites Incorporating Carbon Nanotubes. Macromol. Rapid Commun. 2005, 26 (5), 412−416. (148) Yu, K.; Westbrook, K. K.; Kao, P. H.; Leng, J.; Qi, H. J. Design considerations for shape memory polymer composites with magnetic particles. J. Compos. Mater. 2013, 47 (1), 51−63. 10086


Review

ACS Applied Materials & Interfaces (149) Gupta, A. K.; Gupta, M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 2005, 26 (18), 3995−4021. (150) Mornet, S.; Vasseur, S.; Grasset, F.; Duguet, E. Magnetic nanoparticle design for medical diagnosis and therapy. J. Mater. Chem. 2004, 14 (14), 2161−2175. (151) Marco, D.; Eckhouse, S. Bioerodible self-deployable intragastric implants. US 8864784 B2, 2014. (152) Maitland, D. J.; Metzger, M. F.; Schumann, D.; Lee, A.; Wilson, T. S. Photothermal properties of shape memory polymer microactuators for treating stroke. Lasers Surg. Med. 2002, 30 (1), 1−11. (153) Jiang, H. Y.; Kelch, S.; Lendlein, A. Polymers Move in Response to Light. Adv. Mater. 2006, 18 (11), 1471−1475. (154) Lee, K. M.; Koerner, H.; Vaia, R. A.; Bunning, T. J.; White, T. J. Light-activated shape memory of glassy, azobenzene liquid crystalline polymer networks. Soft Matter 2011, 7 (9), 4318−4324. (155) Dubruel, P., Van Vlierberghe, S., Eds. Biomaterials for Bone Regeneration: Novel Techniques and Applications; Woodhead, Elsevier Science: Cambridge, U.K., 2014. (156) Yang, B.; Huang, W. M.; Li, C.; Lee, C. M.; Li, L. On the effects of moisture in a polyurethane shape memory polymer. Smart Mater. Struct. 2004, 13 (1), 191. (157) Hatakeyama, T.; Quinn, F. X. Thermal analysis: Fundamentals and applications to polymer science; Wiley: West Sussex, U.K., 1999. (158) Niu, G.; Cohn, D. Water Triggered Shape Memory Materials. Sci. Insights 2013, 3 (1), 49−50. (159) Nji, J.; Li, G. A biomimic shape memory polymer based selfhealing particulate composite. Polymer 2010, 51 (25), 6021−6029. (160) Peppas, N. A.; Hilt, J. Z.; Khademhosseini, A.; Langer, R. Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology. Adv. Mater. 2006, 18 (11), 1345−1360. (161) Peppas, N. A.; Bures, P.; Leobandung, W.; Ichikawa, H. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm. 2000, 50 (1), 27−46. (162) Hoare, T. R.; Kohane, D. S. Hydrogels in drug delivery: Progress and challenges. Polymer 2008, 49 (8), 1993−2007. (163) Drury, J. L.; Mooney, D. J. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 2003, 24 (24), 4337−4351. (164) Sun, J.-Y.; Keplinger, C.; Whitesides, G. M.; Suo, Z. Ionic skin. Adv. Mater. 2014, 26 (45), 7608−7614. (165) Calvert, P. Hydrogels for Soft Machines. Adv. Mater. 2009, 21 (7), 743−756. (166) Zhao, X. Multi-scale multi-mechanism design of tough hydrogels: building dissipation into stretchy networks. Soft Matter 2014, 10 (5), 672−687. (167) Sun, J.-Y.; Zhao, X.; Illeperuma, W. R. K.; Chaudhuri, O.; Oh, K. H.; Mooney, D. J.; Vlassak, J. J.; Suo, Z. Highly stretchable and tough hydrogels. Nature 2012, 489 (7414), 133−136. (168) Low, Z. W.; Chee, P. L.; Kai, D.; Loh, X. J. The role of hydrogen bonding in alginate/poly(acrylamide-co-dimethylacrylamide) and alginate/poly(ethylene glycol) methyl ether methacrylate-based tough hybrid hydrogels. RSC Adv. 2015, 5 (71), 57678−57685. (169) Sun, T. L.; Kurokawa, T.; Kuroda, S.; Ihsan, A. B.; Akasaki, T.; Sato, K.; Haque, M. A.; Nakajima, T.; Gong, J. P. Physical hydrogels composed of polyampholytes demonstrate high toughness and viscoelasticity. Nat. Mater. 2013, 12 (10), 932−937. (170) Hu, Y.; Lu, C.-H.; Guo, W.; Aleman-Garcia, M. A.; Ren, J.; Willner, I. A Shape Memory Acrylamide/DNA Hydrogel Exhibiting Switchable Dual pH-Responsiveness. Adv. Funct. Mater. 2015, 25 (44), 6867−6874. (171) Abdul Karim, A.; Loh, X. J. Design of a micellized [small alpha]cyclodextrin based supramolecular hydrogel system. Soft Matter 2015, 11 (27), 5425−5434. (172) Appel, E. A.; del Barrio, J.; Loh, X. J.; Scherman, O. A. Supramolecular polymeric hydrogels. Chem. Soc. Rev. 2012, 41 (18), 6195−6214.

(173) Li, J.; Loh, X. J. Cyclodextrin-based supramolecular architectures: Syntheses, structures, and applications for drug and gene delivery. Adv. Drug Delivery Rev. 2008, 60 (9), 1000−1017. (174) Latude-Dada, G. O.; Simpson, R. J.; McKie, A. T. Duodenal Cytochrome B Expression Stimulates Iron Uptake by Human Intestinal Epithelial Cells. J. Nutr. 2008, 138 (6), 991−995. (175) Ajili, S. H.; Ebrahimi, N. G.; Soleimani, M. Polyurethane/ polycaprolactane blend with shape memory effect as a proposed material for cardiovascular implants. Acta Biomater. 2009, 5 (5), 1519−1530.

10087


Recent Advances in Shape Memory Soft Materials for Biomedical

Recommend Documents