Advances in Functional Chitin Materials: A Review - ACS Sustainable

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Advances in Functional Chitin Materials: A Review Julia L. Shamshina, Paula Berton, and Robin D. Rogers ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.8b06372 • Publication Date (Web): 20 Feb 2019 Downloaded from http://pubs.acs.org on February 25, 2019

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ACS Sustainable Chemistry & Engineering

Advances in Functional Chitin Materials: A Review

Julia L. Shamshina,1,* Paula Berton,2 and Robin D. Rogers3

1 Mari Signum, Mid-Atlantic, 3204 Tower Oaks Boulevard, Rockville, MD 20852, USA 2 Chemical and Petroleum Engineering Department, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada 3 525 Solutions, Inc., 720 2nd Street, Tuscaloosa, AL 35403, USA

Keywords: chitin-based functional materials, films, beads, fibers, hydrogels, hydroxyapatite composites, ionic liquids

Abstract Chitin is a promising natural polymer to produce functional materials due to the attractive combination of abundance, price, favorable biological properties, and biodegradability. However, multiple literature examples often confuse processing of chitosan, the deacetylated version of chitin, due to chitosan’s much higher solubility in traditional solvents. Nonetheless, despite current challenges to solubilize natural chitin, there is still a large body of literature demonstrating multiple ways to manipulate this polymer into materials of desired forms and properties. Here we review one such area where chitin promises both technological superiority and potential for commercial success, the use of chitin in biomedical research. We discuss techniques which have been utilized to process chitin and to prepare chitin-based functional

1

Corresponding Author’ Email address: [email protected]

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materials, particularly in the production of fibers, films, beads, and hydrogels. Emphasis is given to the most recent methods and a compilation of a compelling collection of examples based on current research and existing products. These examples demonstrate the suitability of chitin for production of surgical sutures, wound care materials, tissue engineering biomaterials, and other various biomedical applications.

Introduction Today’s societal reliance on synthetic plastic products is a legacy of World War II, when the US turned to synthetic polymers to help overcome the lack of a native source of polymers such as rubber.1 The combination of investment, innovation, and large scale production has led to plastics becoming essential in many areas of our lives with subsequent increase in plastic production volume from 2 mln metric tons per year in 1950, to over 400 mln metric tons per year in 2015.2 The Global Plastics Market is expected to reach $654 bln by 2020.3 As with many wonder synthetic chemicals and materials of the past, unintended consequences have appeared and now the debate over the sustainability of plastics have become one of the most popular clickbait headlines. Plastic pollution is now considered to be an important environmental problem by the United Nations Environment Program,4 which launched a global campaign to eliminate single-use plastic usage by the year 2022. This means we must again start seeking for alternatives and one wonders if we might go back to the future and use natural polymers for today’s high technology products. According to Porter’s five forces framework,5 several factors should be considered to determine a suitable alternative or ‘substitute product’: consumer opinion, price, quality, function, attributes, and performance. Interesting, though, this framework overlooks the field of “green technologies,” that deals with sustainable raw sources and techniques for making sustainable products. Biopolymers occurring in living organisms can be a suitable alternative, 2 ACS Paragon Plus Environment

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just as they once were when considered by Henry Ford, who pursued a better way to make cars by using the soybean as a source for car body panels. The soybean car was unveiled by Henry Ford on August 13, 1941.6 Biopolymers are chain-like molecules made up of repeating units that vary in length and include polysaccharides (made of sugar units), proteins (made of amino acids), and nucleic acids (made of nucleotides). The makeup of biopolymers determines their characteristics such as stiffness, strength, elasticity, and toughness. Biopolymers are also ‘compostable,’ i.e., there is ‘scientific evidence that these materials can break down (. . .) in a safe and timely manner,’7 completely decomposing in a specified timeframe, with formation of innocuous products. Among biopolymers, the two most abundant in Nature are cellulose (present in lignocellulosic plants) and chitin (present in the exoskeleton of shellfish and insects or in the cell walls of fungi).8,9 Both are structurally similar: cellulose is made of D-glucose units connected by β-(1→4) linkages, while chitin is made of repeated 2-(acetylamino)-2-deoxy-Dglucose units (Figure 1). Chitosan (Figure 1), the deacetylated form of chitin, has also been extensively studied. All three are included in the Environmentally Degradable Plastics List (EDP).10 As of today, many biopolymer-produced materials have already met the expectations on performance, such as for example, moisture sensitivity, strength, and elasticity while for many other improvements are still desired.

Figure 1. Structure of chitin (left), its derivative chitosan (center), and cellulose (right).

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There are multiple successful examples of commercial biomaterials from chitin derivative, chitosan, such as Beschitin W by Unitika, Ltd. Japan,11,12 Syvek Patch® by Marine Polymer Technologies,13 Excel Arrest® by LLC Haemostasis Co.14 A diverse array of cellulose products are also known including Rayon manufactured in the U.S. since 1910 by Avtex Fibers Inc. (formerly FMC Corporation and American Viscose),15 Cellulose Sponge by 3M, and a nanofilament FiloCell additive by Kruger.16 Recently, the strongest biobased cellulose fibers were reported by KTH Royal Institute of Technology.17 Despite modest past successes, in a highly competitive global market, high-value products, rather than commodities, can cause high industrial growth. Introduction of any competitor to plastics in the commodities market will suffer from lack of economy of scale and price. However, materials with very high market value (e.g., materials destined for medical applications) could make breakthroughs with the right set of properties. For example, chitin and its derivative, chitosan, can be used for producing sutures, wound healing gauges, drug delivery vehicles, and scaffolds.18,19 These polymers are biocompatible and can serve as a 3D tissue growth matrix20 due to their structural similarity with N-glycosaminoglycans, which are essential to life and important components of connective tissues and are involved in a variety of extracellular and intracellular activities.21,22 Chitin and chitosan are also wound healing accelerators,23 promote rapid dermal regeneration,24 while demonstrating no adverse effect on cell proliferation on wound surfaces, with fast re-formation of epidermal tissues. It has been shown that a porous chitin matrix filled with pre-proliferated epidermal cells (Unitika’s Beschitin W) formed a complete epidermis when attached to the wounds, followed by decomposition of the chitin matrix as epidermis cells proliferate.25 Still, chitin presents challenges for its isolation, solubilization, and manipulation to generate materials of desired forms and properties.


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This review will focus on the preparation of chitin materials (mostly for potential medical uses and packaging for medical devices) to demonstrate the potential of chitin in emerging applications. We will also concentrate this review in the use of chitin and not chitosan, due to the major differences in the properties of the final materials, and our desire to understand how underivatized natural polymers can be more widely used in material applications. We have purposely restricted our review to the most recent and compelling collection of examples and the most often used chitin architectures, thus this review is not an exhaustive list of chitinbased materials.

Chitin Isolation In the context of Green Chemistry and Sustainability, we should point out that the use of chitin in any application today is hampered by the method it is isolated. Chitin is isolated primarily from crustacean biomass where it exists in a matrix of minerals (calcium carbonate and phosphate) and proteins, with small amount of lipids (ca. unsaturated fatty acids) and astaxanthin;26 other biomass sources such as fly larvae, squid pen or fungi present significantly less volume supply.27,28,29 Chitin materials are typically prepared from one or the other chitin types: commercially available chitin obtained by pulping30 or chitin produced by ionic liquid extraction.31 At the same time, the method of chitin isolation dramatically affects whether the material can even be prepared, and what properties it will exhibit if it can.32 This is because the traditional method of chitin isolation, pulping, results in variable reduction in molecular weight (MW), non-uniform chain scissions, and unwarranted deacetylation (decrease in degree of acetylation, DA), producing a polymer of low quality, with inconsistent characteristics.33 Specifically, pulping includes demineralization with HCl, deproteinization with NaOH, and a discoloration with organic solvents and/or oxidants, at relatively high temperatures (60-100 °C) for 12-48 h.30,34 Isolation conditions mainly depend 5 ACS Paragon Plus Environment


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on the source and the species, with different sources and types of raw materials requiring custom modifications to the chemical treatment (i.e., concentrations of NaOH and/or HCl, temperature and time variations) to isolate chitin.33 In this review we will call chitin produced from this commercial technology as “commercial chitin.” Contrarily, no hydrolysis/degradation of the polymer occurs during ionic liquid (IL) extraction, allowing for more effective control over the final product’s physical characteristics such as strength.31,35 In addition, a high degree of acetylation is maintained, greatly expanding chitin’s potential applications.31 Namely, ILs are now used as an alternative for the isolation (via microwave-assisted extraction) of chitin from crustacean biomass.31 The IL 1‐ethyl‐3‐methylimidazolium acetate ([C2mim][OAc]) has been used in combination with microwave energy, to dissolve chitin directly from raw biomass in a physical, rather than chemical, dissolution process.31 Dissolution of chitin is based on the disruption of the interand intramolecular hydrogen bonding of chitin and the formation of new hydrogen bonds between the polymer hydroxyl protons and the basic anions of the IL. Thus, separation of the chitin becomes possible with relative efficiency, without using toxic chemicals, and without significant degradation of the natural polymer. This results in a highly acetylated, high MW chitin, unachievable through traditional chemical pulping. The IL solvent alternative belongs to the lowest toxicity category 5 according to GHS classification.36-38 When the chitin is dissolved in the IL, the minerals are not dissolved and are separated by centrifugation of the hot IL/chitin solutions. The chitin is recovered from solution using an anti-solvent (e.g., water) which results in coagulation (regeneration) of the chitin and removal of the IL solvent. Proteins and fatty acids remain in the water-IL mixture after coagulation and are removed during the IL recycle. In this review we will call chitin produced from IL extraction of crustacean shells and subsequent regeneration as “IL-regenerated chitin.”


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While there is a number of reports of the use of chitin obtained by other methods,34,39-45 including milder pulping reagents or use of enzymes, we are unaware of use of these types of chitin for material preparation. Future efforts in these areas may lead to a viable alternative and replace existing pulping or ionic liquid extraction.

Chitin-Based Materials and Composites Chitin Fibers Even though the global textile market uses natural fibers (e.g., cotton), fibers of synthetic origin (e.g., polyester, acryl, aramid, elastin, polyamide, polyacrylonitrile, rayon)46 prevail significantly. By far the largest segment in this field are synthetic fibers which account for about half of all fiber usage.47 Among those, nylon, polyester, acrylic and polyolefin cover largest end-user segment of the global synthetic fiber production, 98% by volume. Quite a significant production volume relates to fibers made by chemical transformation of natural polymers (e.g., regenerated cellulosics: viscose, lyocell, triacetate). In this regard, chitin fiber for the textile market would be game changing because it is natural, and biodegradable, therefore concealing the increased concern for human health and environment. Indeed, textiles are the third (after packaging and food) largest end-user segment of the global Bioplastics & Biopolymers market, estimated to reach $6.95 billion by the end of 2018 and projected to almost double in 5 years with a compound annual growth rate (CAGR) of 16.5%.48 The fastest growing niche is medical textiles and implantable medical textiles, for a wide variety of surgical applications. In addition, when considering fibers for medical applications, chitin is a polymer of interest because it is biologically inert and neither causes nor promotes complications or tissue reaction, properties important for an ideal implantable textile. The ideal implantable textile should also be strong, and lose strength at the same rate that the tissue gains strength.49 In this regard, chitin 7 ACS Paragon Plus Environment


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fibers or composites with cotton or other natural and/or synthetic polymers (e.g., cellulose, bamboo, polylactic acid (PLA)), with or without additives (vitamins, existing drugs, etc.) would be ideal candidates. The preferable technique for producing homogeneous chitin fibers is solution processing, but since chitin is insoluble in most common solvent systems, ‘special’ solvent systems have been developed for chitin dissolution and extensive reviews cover this topic.39,50 From solution, chitin fibers are produced by extrusion, where the polymer dope is fed out of a mono- or multifilament extruder into a coagulation bath. Both wet-jet and dry-jet spinning are possible: the dissolved polymer is either extruded into a liquid coagulation bath directly, with extruder nozzle to be under the water surface (wet spinning) or into an air gap and then into a coagulation bath (dry spinning). Inorganic bases (e.g., sodium hydroxide (NaOH), calcium thiocyanate (Ca(CNS)2), calcium iodide (CaI2), calcium bromide (CaBr2), calcium chloride (CaCl2), and lithium thiocyanate (LiCNS)) were shown to be capable of disrupting the chitin hydrogen bonding as early as 1927.51-53 These solvents were the earliest ones from which the spinnability of chitin was evaluated. Weimarn showed that a thread-like precipitate of chitin can be formed from these solvents upon coagulation in ethanol.51 Although it was found that LiCNS worked the best, the resultant filaments (‘ropy-plastic’) were not continuous and could not be classified as fibers. Clark and Smith in 1936 extended Weimarn’s work reprecipitating chitin from its LiCNS aqueous solution in the form of filaments into water-acetone as coagulant, but now applying some stretching to these filaments during their formation.54 Although still not continuous, the filaments were able to develop a considerable degree of orientation after stretching. Clark and Smith also proved these systems caused depolymerization, and LiCNS was difficult to remove from the prepared material.


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Halogenated (perfluorinated or chlorinated) or highly acidic polar solvent systems have been used for the dissolution of chitin (dichloroacetic acid, trichloroacetic acid, formic acid or combination of these). Often these have been mixed with various volatile organic solvents (VOCs) as co-solvents to reduce viscosity (e.g., methylene chloride, chloroform, isopropyl ether) before extrusion.55-58 Thus, trichloroacetic acid with methylene chloride have been used to prepare spinning dope (Table 1, Entry 1),55 which was extruded into acetone or methanol as coagulants.55 Various solvent systems and coagulants have been used. Austin prepared chitin fibers from chitin in trichloroacetic acid, dichloroacetic acid or combination of such, mixed with isopropyl ether for viscosity reduction, coagulated using ethylacetate, isopropyl ether, or acetone (Table 1, Entry 2).56,57 Tokura et al. employed solutions of chitin in formic acid/dichloroacetic acid mixtures followed by wet spinning into ethylacetate coagulant (Table 1, Entry 3).59 It is important to note that in all above-mentioned examples removal of acids was problematic, and required either boiling in water, or treatment with ethanolic NaOH for neutralization of the excess of acids, followed by washing and drying. In addition, due to high acidity of the solvents, the dissolution was accompanied by acid-catalyzed depolymerization, sacrificing the quality (and thus, strength) of resultant fibers.57 Because of the solubility of chitin in N,N-dimethylacetamide/lithium chloride (DMAc/LiCl)60-62 or N-methyl-2-pyrrolidone/lithium chloride (NMP/LiCl),63 also used for cellulose dissolution,64 these systems were also utilized in the preparation of chitin fibers, yet removal of LiCl proved problematic (Table 1, Entry 4).65 In these systems, the Li+ ion of LiCl is coordinated with the carbonyl groups of DMAc (or NMP) forming a complex in which the lithium cation is strongly bound to the amide carbonyl oxygen and the chloride anion is thus involved in the dissociation of the chitin hydrogen bonds,64,,66 and this complex is hard to remove.



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Since 2001, ILs have been extensively used as solvents for chitin, which has shown to be soluble

in

1-butyl-3-methylimidazolium

chloride

([C4mim]Cl)67-69

and

acetate

([C4mim][OAc]), and 1-ethyl-3-methylimidazolium chloride ([C2mim]Cl) and acetate ([C2mim][OAc]), among others. The ability of the ILs to both extract chitin of high MW from biomass and dissolve this regenerated polymer was successfully utilized by Qin et al. who prepared fibers through dry-jet spinning of either shrimp shell extract or IL-regenerated chitin in [C2mim][OAc] IL (Table 1, Entry 5).31 The process involved dissolving either shrimp shells (followed by centrifugation) or regenerated polymer dissolution in [C2mim][OAc] and then extrusion, washing and air-drying. Using the same high MW chitin, the same IL, and the same technique, allows not only the production of “pure chitin” fibers, but also co-dissolution of chitin with a second polymer, to generate composites. Thus, chitin was blended with PLA (Table 1, Entry 6) to impart strength, by co-dissolution in the IL, and extrusion into water coagulation bath.70 Similarly, composite fibers of chitin with calcium alginate (Table 1, Entry 7)71 for use as wound care dressings were prepared by co-dissolution of chitin with alginic acid followed by extrusion into calcium chloride aqueous solution; wound healing patches prepared from chitin-calcium alginate fibers demonstrated excellent biocompatibility, fast reepithelization, and ‘early healing’ ability. The Rogers’ group also demonstrated the preparation of fibers on nanoscale, using a large scale electrospinning setup for electrospinning of chitin biopolymer.72,73 This equipment was used for the electrospinning of crustacean biomass solution, chitin, and chitin composites with other biopolymers (lignin, cellulose) or synthetic polymers (PLA).74-76 A separate book chapter has been dedicated to the analysis of these studies.73 The commercial chitin was not suitable for electrospinning in any of these studies.

Table 1. Preparation of chitin-based films and potential applications 10 ACS Paragon Plus Environment

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Entry

Chitin or Chitin Biomass Type Solubilization

1

Commercial chitin (biomass Trichloroacetic source: Pink acid/methylene Crab, hard chloride shell)

2

Commercial chitin (biomass Formic acid – source: Alaska dichloroacetic King Crab acid shell)

3

Commercial Formic acidchitin (biomass dichloroacetic source: Queen acid Crab shell)

Material Preparation 1. Pulping chitin from crab shell; 2. Solubilization in trichloroacetic acid and methylene chloride; 3. Mono- or multifilament extrusion; 4. Coagulation in methanol or acetone; 5. Acids neutralization with an aqueous potassium hydroxide; 6. Washings with DI water; 7. Drying under vacuum. 1. Swelling chitin powder in formic acid, followed by freezing and melting; 2. Dispersion of resultant gel in dichloroacetic acid; 3. Addition of isopropyl ether; 4. Filtration from undissolved materials; 5. Spinning through into a coagulation bath (1st/2nd coagulation bath: ethylacetate/ethanol; isopropyl ether/acetic acidethanol mixture; acetone/ acetic acid-ethanol mixture; ethylacetate/water; ethylacetate-isopropyl ether/water; 6. Washings with boiling water to remove formic acid and dichloroacetic acid; 7. Air-drying. 1. Dissolution: a) Chitin powder swelling in NaOH and sodium dodecylsulfate then freezing; b) Melting with formation of a gel; c) Gel solubilization in formic aciddichloroacetic acid mixture; 2. Spinning (no stretching bath) into ethylacetate coagulation bath; 3. Washings with ethanolic NaOH to remove acids,

Application Ref.

Surgical suture

55

Not reported

56

Not reported

59



4.

4

Commercial chitin (biomass source: crab, protein-free, DMAc/LiCl degree of polymerization (DP) 678, MW 137,000 Da)

6

7

Commercial chitin; shrimp [C2mim][OAc] shell biomass

IL-regenerated chitin (biomass source: shrimp shell; [C2mim][OAc] regenerated with [C2mim][OAc]) IL-regenerated chitin (biomass source: shrimp [C2mim][OAc] shell; regenerated with [C2mim][OAc])

followed by washing with neat ethanol; Air-drying.

1. Dissolution in 5% DMAcLiCl; 2. Fiber extrusion into water Not coagulation bath; reported 3. Washing in hot water; 4. Air-drying. 1.

5

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2.

3. 4. 1. 2.

3. 4. 1. 2.

3. 4.

Dissolution of shrimp shell biomass or chitin (commercial) in [C2mim][OAc]; Monofilament fibers production through a continuous dry wet-jet spinning process; Washings with water; Air-drying. Co-dissolution of chitin and PLA in [C2mim][OAc]; Monofilament fibers production through a continuous wet-spinning process; Washings with water; Air-drying. Co-dissolution of chitin and alginic acid in [C2mim][OAc]; Monofilament fibers production through a continuous wet-spinning process into aq. calcium chloride coagulation bath; Washings with water; Air-drying.

65

Not reported

31

Not reported

70

Wound care 71 dressings

Chitin Beads The recent increase of studies of plastic microbeads in personal care products and products for biomedical research has led to the use of multiple synthetic polymers (e.g., PLA, poly(glycolic acid), poly(ε-caprolactone)) for their production. However, the Federal Food, Drug, and Cosmetic Act banned both manufacture (since July 1, 2017) and import (since January 1, 2018) of all rinse-off microbeads-containing cosmetics as a consequence of their 12 ACS Paragon Plus Environment

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environmental pollution.77 Starting July 2018 personal care and cosmetics products containing plastic microbeads have been restricted for their manufacture, import, and sale. Moreover, microbeads in non-prescription drugs are planned to be banned in 2019.77 The reason for the decision is that solid plastic microbeads do not naturally decompose, while the size of the microbeads makes them difficult to eliminate from the environment. On the other hand, chitin offers a bio-based alternative to synthetic polymers due to its properties (non-toxic, biocompatible, biodegradable, and short-term accumulation in nature) for use in cosmetics and personal care products, ranging from shower gels to scrubs, to toothpastes. There are scarce examples of beads prepared from chitin. Examples include beads made of commercial chitin, additionally purified by treatment with 50% NaOH at room temperature for 7 days prior to use (Table 2, Entry 1).61 Chitin was dissolved in DMAc/LiCl and droplets of chitin solution were added to anti-solvent (ethanol) from a syringe using a syringe pump. After that, beads were washed in deionized water or ethanol and vacuum-dried. The beads were sequentially carboxymethylated, and the surface area was not determined. Unfortunately, such drying techniques while removing the solvent (water or ethanol) by evaporation, normally results in strengthening of the intermolecular hydrogen bonding between the biopolymer chains, which leads to collapse of the interchain pores, shriveling, and lowering of surface areas. In another example, chitin microbeads were prepared from high MW chitin regenerated using the IL [C2mim][OAc] (Table 2, Entry 2),78 by coagulating the chitin re-dissolved in the IL in polypropylene glycol (PPG, MW 2000) at 60 °C, followed by rapid stirring in a coagulation bath, washing and supercritical CO2 (sc-CO2) drying. Chitin beads were microand mesoporous with a large specific surface area of 24.93 m²/g.79 It is important to note that while uniformly-sized beads with a spherical shape were prepared from the IL-extracted chitin, mostly flakes were the product from commercial chitin, with only some beads formed. 13 ACS Paragon Plus Environment


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Table 2. Preparation of chitin-based beads and potential applications Entry Chitin or Chitin Biomass Type Solubilization

1

Commercial chitin

2

IL-regenerated chitin (biomass source: shrimp [C2mim][OAc] shell; regenerated with [C2mim][OAc])

DMAc/LiCl

Material Preparation 1. Chitin treatment with NaOH; 2. Chitin dissolution in 5% (w/v) DMAc/LiCl; 3. Syringe pump addition into water or ethanol; 4. Washings with water or water then acetone; 5. Vacuum drying. 1. Dissolution of chitin in [C2mim][OAc]; 2. Syringe pump addition into polypropylene glycol (PPG MW 2000); 3. Washings with water; 4. Soaking in ethanol (anh.); 5. Sc-CO2 drying; 6. Active (caffeine) loading and release.

Application Ref.

Wound dressing

61

Cosmetic release

78

Chitin Films Two main industries that would benefit from chitin films are packaging and medical devices. Packaging is the largest end-user segment of the global biopolymer market (over 65% market size), and most of the demand is generating from the need for eco-friendly packaging, since packaging normally is a single-use product. Food packaging protects food, stops moisture loss, and extends the period the food stays fresh. Chitin films are very promising in this regard because they allow a controlled water-vapor transmission rate (WVTR), i.e., controlled water loss from food. In the biomedical industry, chitin films are also excellent candidates as wound dressing of dry or light exudation wounds, again due to controlled WVTR.80 They prevent both quick drying (producing scars) or exudates accumulation (retarding healing). Chitin films are generally prepared through the dissolution of chitin in a suitable solvent system (typically the same solvent systems described above for the preparation of chitin fibers), casting onto a glass plate, coagulation using an anti-solvent with formation of a hydrogel, and 14 ACS Paragon Plus Environment

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then drying by air-drying, press-drying or using vacuum. Alternatively, chitin solutions can be placed into molds followed by coagulation and cold pressing prior to drying. Chitin films have been prepared from the solution of the biopolymer in NMP/LiCl or DMAc/LiCl (Table 3, Entry 1) by casting the filtrate onto a glass plate followed by coagulation using water, acetone, methylethylketone, methanol, ethanol, propanol, or butanol; drying was done at either ambient or elevated temperatures.62 Similarly, chitin films were prepared through chitin solubilization in DMAc/LiCl, molding and gelation instead of casting, alcohol (ethanol or isopropanol) coagulation, and cold pressing and oven-drying (Table 3, Entry 2).81 As with chitin fibers, it is difficult to completely remove the LiCl salt from the resulting material. Methods using aqueous NaOH/urea eutectic have also been used extensively50 for the preparation of chitin materials, by freeze thawing cycles.82,83 However, the presence of NaOH in the system could lead to deacetylation and results in the formation of chitosan.84 The films prepared using this system were prepared with different applications in mind, from packaging with improved gas barrier properties to cell carriers. Commercial chitin was dissolved in aqueous NaOH/urea eutectic mixture by repeated freeze/thaw treatment (the so-called freezing/thawing method).85,86 The chitin solution was molded as a thin film into a dish, placed into a 50 °C oven for 1 h to form a gel, which then was immersed into distilled water for washing, and dried in the air (Table 3, Entry 3).85 Chitin films obtained by this method are often brittle and have to be plasticized with glycerol.85 In order to fabricate films with improved gas-barrier properties, Duan et al. cast chitin films from NaOH/urea but coagulated them in salt solutions, acids, and organic solvents instead of pure water (Table 3, Entry 4).86 When acid and aqueous salts (5 wt% aq. H2SO4, 5 wt% aq. CaCl2) were used to fabricate chitin films, the resulting films were not homogeneous and fractured during the drying process. On the other hand, films coagulated in organic coagulants (ethanol and 45 wt% aq. DMAc) exhibited good mechanical properties and optical 15 ACS Paragon Plus Environment


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transmittance although required plasticization with glycerol. Films demonstrated improved gas barrier properties, indicating great potential as packaging materials.86 Other examples include the preparation of neat chitin films using ILs as solvents. As mentioned above, the ILs can also be used for chitin isolation, producing a high MW polymer, but can also be used to prepare films from lower MW commercial chitin. The high MW ILregenerated chitin was dissolved in the IL [C2mim][OAc] and cast onto a glass plate prior to washing, resulting in pure chitin films (Table 3, Entry 5), which were press-dried.87 The same solvent was used for casting composite flexible chitin films with graphene/graphene oxide, via dispersion of graphene in the chitin/IL solution followed by casting, washing, and drying (Table 3, Entry 6).88 We would like to note here that the film cast from the commercial source of chitin yielded a fragile, web-like film which immediately fractured after casting due to its low molecular weight. Although still a proof-of-concept study, such films could be used in electrochemical devices.

Table 3. Preparation of chitin-based films and potential application Entry


1

Commercial chitin (biomass DMAc/LiCl or source: red crab NMP/LiCl shells)

2

Commercial chitin (biomass source: DMAc/LiCl Philippine blue swimming crab)

Material Preparation

Application

1. Chitin solubilization in DMAc/LiCl or NMP/LiCl; 2. Filtration from undissolved material; 3. Filtrate casting onto a glass plate; Not reported 4. Air-drying for 1 h; 5. Coagulation in water, ethanol or acetone bath; 6. Washings with water, ethanol or acetone; 7. Air-drying 1. Crab shells treated with NaOH, HCl, and H2O2 to remove impurities; Not reported 2. Chitin solubilization in 5% (w/v) DMAc/LiCl;

Ref.

62

81


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3

Chitin (commercial source)

NaOH/urea (aq)

4

Commercial chitin

NaOH/urea (aq)

5


3. Solution molding with gel formation; 4. Ethanol or isopropanol soaking (coagulation); 5. Cold pressing; 6. Oven-drying; 7. Second ethanol or isopropanol soaking; 8. Cold pressing. 1. Chitin solubilization in NaOH/urea (aq) using freezing-thawing method; 2. Gelation at 50 °C; 3. Washings with water; 4. Air-drying; 5. Plasticization with glycerol; 6. Air-drying. 1. Chitin treatment with NaOH, HCl, NaClO and NaOOCCH3, to remove impurities; 2. Chitin solubilization in NaOH/urea (aq) using freezing-thawing method; 3. Degassing through centrifugation; 4. Casting onto glass plate; 5. Coagulation in 5 wt% H2SO4 (aq); 5 wt% CaCl2 (aq); 45 wt% DMAc (aq); or ethanol; 6. Washings with water; 7. Air-drying; 8. Plasticization with glycerol (selected films). 1. Chitin extraction using [C2mim][OAc]; 2. Chitin regeneration; 3. Dissolution of chitin in [C2mim][OAc]; 4. Casting onto a glass plate; 5. Coagulation with water; 6. Washings with water to remove the IL; 7. Press-drying (films) or sc-CO2 drying; 8. Loading with active (caffeine) and release.

Not reported

85

Packaging material

86

Not reported, potential usage as hydrogel 87 dressings in drug delivery and packaging



6


Page 18 of 44

1. Chitin extraction using [C2mim][OAc]; 2. Chitin regeneration ; 3. Dissolution of chitin in [C2mim][OAc]; Electrochemi 4. Suspending graphene cal device or graphene oxide; 5. Casting onto a glass plate; 6. Coagulation into water; 7. Washing with water; 8. Air-drying.

88

Hydrogels Hydrogels are biomaterials designed first as ophthalmic devices and, since then, developed into a large variety of products for the medical, biological, and pharmaceutical fields.89 They are

used

for

soft

contact

lenses,

drug

delivery

devices

to

the

eye,

tissue

engineering/regeneration, cell immobilization, drug delivery, and wound dressings. Commercial products (made of carboxymethylcellulose, polyols, and sulfonated copolymers) include Granugel® (ConvaTec), Intrasite Gel® (Smith & Nephew), Purilon Gel® (Coloplast), Aquaflo™ (Covidien), and Woundtab® (First Water).90 Hydrogels vary by chemical composition and methods of gelation ranging from ‘physical’ gels to chemically cross-linked networks. The main common attribute of hydrogels is a gel-like network containing both a liquid phase (usually water) and a solid phase, while their shapes vary from beads, films, nanoscale architectures, etc.89 Chitin has great potential in hydrogels as medical devices since, besides the properties mentioned in the previous subsections, it controls cell-signaling (cell function), accelerates formation/regeneration of the extracellular matrix, promotes fibroblast proliferation, granulation, and vascularization, reduces inflammatory pain, is capable of mineralization for bone repair, and is a stimulator of cell proliferation and tissue organization.91 Normally, the methods of preparation of chitin hydrogels include the dissolution in an appropriate solvent, as noted above for films, followed by coagulation in anti-solvent and 18 ACS Paragon Plus Environment

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washing. Hydrogels can be made ‘as is’ or be surface-deacetylated and functionalized.92 Commercial chitin (practical grade from crab shells) was dissolved in DMAc/LiCl (at 1 wt% and 1.85 wt% concentration), and cast in Petri dishes followed by overnight gelation at room temperature, followed by extensive washing of the gels from DMAc/LiCl with distilled water resulting in solid chitin hydrogels in the form of cylinders (Table 4, Entry 1).93 These hydrogels were then exposed to sc-CO2-atmosphere followed by rapid depressurization, for production of more porous structures from hydrogels, similar to foams. In another example, hydrogels and hydrogel beads were formed using commercial chitin powder and the same solvent system but were washed using water, ethanol, or acetone, with ethanol found to be the optimal anti-solvent (Table 4, Entry 2).94 Similarly, NMP/LiCl was used to dissolve low MW chitin (MW 76569 g/mol) at various concentrations and after complete dissolution, the chitin solution was contacted with water vapors as an anti-solvent in a fabrication chamber, to produce chitin hydrogels (Table 4, Entry 3).95 The same system was also used for casting solutions in Petri dishes followed by overnight gelation and coagulation and washing using water, ethanol, or acetone (Table 4, Entry 2).94 Chang et al. used aqueous NaOH/urea as a solvent, and the freeze-thawing method to solubilize chitin (Table 4, Entry 4).96 These hydrogels, however, were weak and in order to make them stronger the addition of epichlorohydrin cross-linker was required. These hydrogels made of chitin were prepared for drug delivery applications and biocompatibility tests were passed.96 Both above-mentioned dissolution systems, DMAc/LiCl and aqueous NaOH/urea, were used for composite hydrogels of chitin with carbon nanotubes for potential use as tissue scaffolds (Table 4, Entry 5), however, similarly to a previous example (Table 4, Entry 4), the hydrogels formed were weak. These hydrogels demonstrated cell adhesion and enhanced cell



Page 20 of 44

proliferation (neuronal cells and Schwann cells) in vitro,97 and showed good biocompatibility and hemocompatibility, without signs of cytotoxicity or neurotoxicity.97 Tamura et. al. (Table 4, Entry 6) used the dissolution of commercial chitin in calcium chloride dihydrate-saturated methanol (CaCl2-methanolic solution). The chitin hydrogels were prepared by adding a large excess of water to the chitin solution, followed by filtration and then dialysis to remove the methanol and calcium ions.98 There are also numerous examples of preparation hydrogels using ILs. The initial report of preparation of hydrogels through the dissolution of neat commercial chitin in the IL [C4mim][OAc] was reported in 2008, when Wu et al. prepared chitin hydrogels from commercial chitin using a cold mold pressing process (Table 4, Entry 7),99 followed by extensive washing with deionized (DI) water to remove the IL. The Rogers’ group used the IL [C2mim][OAc] for chitin dissolution to prepare hydrogels from high MW chitin recovered from biomass using the same IL (Table 4, Entry 8), for drug delivery applications. The preparation was done through solution molding followed by water coagulation and washing.100 The IL 1-allyl-3-methylimidazolium bromide ([Amim]Br) was also shown to be useful to prepare hydrogels from commercial chitin which was either swollen or dissolved, depending on its concentration in the IL. When chitin was mixed with the IL at high concentration (7%), the IL swelled the polymer and induced its gelation at room temperature (Table 4, Entry 9).101 In another example, the same IL was used to dissolve lower concentrations of chitin (up to 5%), and the solution was gelated either using chitin alone, or as a mixture with microcrystalline cellulose in [C4mim]Cl to form a homogeneous mixture (Table 4, Entry 10).102 The solution was molded and kept at room temperature until gelation, forming hydrogels and films.


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Table 4. Preparation of chitin-based hydrogels and potential application Entry


1

Commercial chitin

2

Commercial chitin

3

Commercial chitin (low MW)

4

Commercial chitin

5

Commercial chitin

Material Preparation

1. Chitin dissolution in 6% (w/v) DMAc/LiCl; 2. Solutions cast in Petri dishes and allowed to stay DMAc/LiCl at room temperature overnight; 3. Washings with water or methanol; 4. Sc-CO2 drying. 1. Chitin treatment with NaOH and HCl (chitin purification); 2. Chitin dissolution in 5% (w/v) DMAc/LiCl; or 3. Chitin dissolution in 5% (w/v) NMP/LiCl; DMAc/LiCl or 4. Gel cast in tubes (or slowly dropped) and coagulation NMP/LiCl in water, acetone, or diethyl ether; 5. Washings with water (hydrogels), acetone, or diethyl ether (solventsaturated gels); 6. Vacuum drying (beads). 1. Chitin dissolution in 5% (w/v) NMP/LiCl; 2. Coagulation by water NMP/LiCl vapor in a fabrication chamber. 1. Chitin solubilization in NaOH/urea (aq) using NaOH/urea freezing-thawing method; 2. Epichlorohydrin addition (aq) (cross-linking); 3. Washings. 1. Chitin treatment with NaOH and NaClO2 to remove impurities; 2. Chitin dissolution in 5% (w/v) DMAc/LiCl; or DMAc/LiCl 3. Chitin and carbon and nanotubes mixing in NaOH/urea NaOH/urea (aq) and (aq) solubilization using freezing-thawing method; 4. Gel cast and coagulation in ethanol; 5. Washings with water.

Application

Ref.

Not reported

93

Not reported

94

Not reported

95

Not reported

96

Neuronal growth substrate

97



6

7

8

9

10

Commercial chitin (α-chitin); β-chitin isolated from squid pen using NaOH (aq) and HCl (aq)

Calcium chloride dihydrate methanol (CaCl2MeOH)

Page 22 of 44

1. (α-Chitin) Suspension of chitin in solution of CaCl2MeOH and reflux for several hours with stirring; 2. Addition of water with vigorous stirring 3. Filtration to collect chitin precipitate; 4. Dialysis against distilled water to remove the calcium ions and methanol; in Not reported or 1. (β-Chitin) Suspension in distilled water; 2. Subjecting suspension to a high-speed mechanical agitation in a Warring blender; 6. Repetition (5 times) by the stepwise addition of distilled water, until a homogeneous gel was formed.

Commercial 1. Chitin dissolution in chitin (biomass [C4mim][OAc]; source: α-chitin [C4mim][OAc] 2. Cold mold pressing into from crab; βhydrogel film; chitin from squid3. Washings with water. pen) IL-regenerated 1. Dissolution of chitin in chitin (biomass [C2mim][OAc]; source: shrimp 2. Gelation; [C2mim][OAc] shell; regenerated 3. Washing with water; with 4. Loading with active [C2mim][OAc]) (indigo dye) and release. 1. Preparation of homogeneous solution of chitin in [Amim]Br; 2. Preparation of solution of Commercial cellulose in [C4mim]Cl; chitin (biomass [Amim]Br 3. Mixing both solutions; source: crab 4. Film casting by cold mold shells) pressing; 5. Coagulation with water; 6. Washings (hydrogels); 7. Drying (films). 1. Swelling/dissolution of Commercial chitin powder in chitin (biomass [Amim]Br; [Amim]Br source: crab 2. Gelation at room shells) temperature; 3. Washing with water.

Not reported

98

99

Potential in 100 drug delivery

Not reported

101

Not reported

102


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Composite Chitin Materials as Bone Engineering Scaffolds The market for global tissue engineering was estimated to be around $5 billion in 2016, and is expected to grow to $11.5 billion by 2022, due to increasing volume of tissue repair solutions such as in vitro dental implants, scaffolding, transplants, and other 3D tissue engineering solutions.103 The materials for preparation of bone engineering scaffolds should be biocompatible in order to be well integrated in the host’s tissue without eliciting an immune response, interconnectedly-porous with relatively large pore sizes to allow cell in-growth and cell distribution throughout the structure, allow cellular adhesion and proliferation, and be osteoinductive. Materials should also be mechanically strong and in vitro biodegradable. Synthetic biodegradable polymers such as poly(a-hydroxy acids), poly(e-caprolactone), poly(propylene fumarates), poly(carbonates), poly(phosphazenes), and poly(anhydrides) are most widely used.104 Chitin materials are ideal as bone graft substitutes, because, besides the properties previously discussed, they can be made into composites with hydroxyapatite (HAp), the main mineral component of bone and a naturally occurring osteoconductive mineral.105 It has been demonstrated that HAp can be made into composites with chitin of different architectures, which can be achieved using both non-solubilized chitin (dispersions) or chitin solutions (Table 5). In place of application, we have noted the resultant architectures in Table 5. Wan et al.106 (Table 5, Entry 1) dispersed HAp in DMAc/LiCl, followed by the addition of commercial chitin and stirring the mixture at low temperature for about 4 days. The uniformly-dispersed HAp in chitin solution was then filtered and cast into molds, followed by gelation. Gels were washed in DI water to remove residual LiCl and DMAc, after which the materials were air-dried to produce chitin-HAp flexible films for potential applications as hard tissue substitute material. Ge et al.107 (Table 5, Entry 2) has fabricated these same chitin-HAp films with the exception that the films were lyophilized rather than air-dried. The resulting 23 ACS Paragon Plus Environment


Page 24 of 44

films showed cytocompatibility, cell proliferation, and promoted the in-growth of surrounding tissues. The simplest method for potential bone regeneration applications, included dispersion of nano-HAp particles in chitin solutions followed by preparation of hydrogels. In this method, chitin is used as a polymeric matrix for nano-HAp (Table 5, Entry 3). Thus, chitin/nano-HAp hydrogels have been manufactured using the chitin solubilized in an 8 wt% NaOH/4 wt% urea/88 wt% water system using the freezing/thawing method.108 Nano-HAp particles were uniformly dispersed in chitin solution followed by cross-linking of chitin polymer with epichlorohydrin (ECH). Using this strategy, strong hydrogel scaffolds were generated, which demonstrated good cell adhesion and cell proliferation. Jayakumar et al.109 (Table 5, Entry 4) showed that HAp does not need to be incorporated within the films, and that surface of the chitin hydrocolloid films allows the mineralization of HAp in situ. Chitin dissolution in calcium chloride dihydrate in methanol (CaCl2-MeOH), coagulation in distilled water, blender homogenization, dialysis, and casting were conducted. The resultant chitin films were dried under pressure at room temperature. The chitin membranes were soaked in a simulated body fluid solution containing NaCl, KCl, CaCl2, MgCl2, NaHCO3, K2HPO4, and Na2SO4. A similar approach was followed by Madhumathi et al.110 who prepared hydrocolloid films through suspension of commercial chitin powder in water with blending followed by casting (Table 5, Entry 5). These hydrocolloid films were dried under pressure at room temperature, and sequentially soaked in CaCl2 and ammonium hydrogen phosphate (Na2HPO4) solutions; these soaking cycles were repeated 3-5 times. Films were then washed in DI water and air-dried. In both examples (Table 5, Entries 4 and 5), HAp was formed on the surface of the chitin films. He et al. (Table 5, Entry 6)111 prepared chitin solution in NaOH/urea, molded, coagulated with ethanol, washed with DI water, and plasticized resultant films with glycerol. Then the 24 ACS Paragon Plus Environment

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resultant films were soaked in calcium chloride and then ammonium hydrogen phosphate, followed by treatment in the NH3·H2O atmosphere, to form HAp in situ on the surface of chitin films. After fabrication, the films were rinsed with deionized water, again soaked in glycerin aqueous solution, and dried under vacuum. These films demonstrated in vivo histocompatibility, hemocompatibility, and biodegradability, showing improved cell adhesion, proliferation, and differentiation of the osteoblast cells. Kawata et al.112 used commercially available β-chitin as a powder which was initially swelled in NaOH solution, then washed with ethanol and water to obtain a chitin nanofiber hydrogel, which was then immersed into (NH4)2HPO4 and in Ca(NO3)2 and 5 days later vacuum-filtered (Table 5, Entry 7). Calcium phosphate was successfully mineralized on the chitin hydrogel from aqueous (NH4)2HPO4 and Ca(NO3)2 solutions. It was shown that this hybrid hydrogel accelerated mineralization in the subcutaneous tissue with formation of morphological osteoblasts, offering a new scaffold for bone tissue engineering. All of the examples mentioned above demonstrate the suitability of chitin/HAp composites for bone tissue engineering biomaterials. Irrespective of whether the HAp was added in its final form or synthesized in situ, the resulting materials showed good biological activity (osteoblasts could adhere and grow), biocompatibility in vitro and in vivo, histocompatibility, and in vivo biodegradability. These materials show great potential for biomedical applications, as ‘repair’ materials of non-load bearing bone defects.

Table 5. HAp composites with chitin Chitin or Chitin Entry Biomass Material Preparation Material Solubilization Type 1. Chitin treatment with NaOH and HCl (chitin purification); Commercial 1 DMAc/LiCl 2. Hydroxyapatite dispersion in Film chitin DMAc/LiCl (5% w/v); 3. Addition of chitin;

Ref.

106



2

Commercial DMAc/LiCl chitin

3

Commercial NaOH/urea chitin (aq)

4

Commercial chitin (αCaCl2-MeOH and βchitin)

5

Commercial Not chitin (βsolubilized chitin)

6

Commercial NaOH/urea chitin (aq)

4. Stirring in a refrigerated shaking incubator; 5. Filtration and casting into plastic molds; 6. Gelation; 7. Washings with water; 8. Air-drying. 1. Hydroxyapatite dispersion in DMAc/LiCl (5% w/v); 2. Addition of chitin; 3. Stirring in a refrigerated shaking incubator; 4. Filtration from undissolved materials; 5. Casting into plastic molds; 6. Gelation; 7. Washings with water; 8. Freeze-drying. 1. Addition of Ca(NO3)2 into (NH4)2HPO4 to generate nano-HAp; 2. Chitin solubilization in NaOH/urea (aq) using freezing-thawing method; 3. Addition of nano-HAp to chitinNaOH/urea solution; 4. Addition of ECH as cross-linker; 5. Gelation; 6. Washings with water. 1. Suspension of chitin powder in CaCl2MeOH; 2. Reflux for 6 h, followed by filtration; 3. Addition of chitin solution to distilled water; 4. Precipitation of homogenized gel; 5. Dialysis of homogenized gel against distilled water until no calcium ion is detected; 6. Casting; 7. Drying; 8. Soaking in a simulated body fluid solution containing NaCl, KCl, CaCl2, MgCl2, NaHCO3, K2HPO4 and Na2SO4; 9. Air-drying. 1. Suspension of commercial chitin in water; 2. Gelation by blending; 3. Casting; 4. Soaking in CaCl2 and Na2HPO4 solutions; soaking cycles repeated 3-5 times; 5. Washing with DI water; 6. Air-drying. 1. Chitin treatment with NaOH, HCl, and H2O2 to remove impurities;

Page 26 of 44

Film

107

Hydrogel 108

Film

109

Film

110

Film and 111 hydrogel


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7

2. Chitin solubilization in NaOH/urea (aq) using freezing-thawing method; 3. Degassing through centrifugation; 4. Molding; 5. Coagulation with ethanol; 6. Washing with DI water; 7. Plasticization with glycerol; 8. Soaking of chitin films in CaCl2, and Na2HPO4 aqueous solutions; 9. Vacuum drying. 1. Suspension of chitin powder in DI water; 2. Gelation; 3. ‘Filtration’ of the gel; Film 4. Drying under pressure at room temperature (with formation of films); 5. Soaking of chitin films in CaCl2, and Na2HPO4 aqueous solutions.

Commercial Not chitin (βsolubilized chitin)

112

Outlook: Commercial Deployment The chitin market is expanding at a fast pace and forecasted to triple to $2,941 million by 2027. Yet, while chitosan has been extensively studied by biomedical research communities as a bona fide raw source for the preparation of biomaterials, chitin is not utilized to its full potential. At present, wide-scale use of chitin is being limited by the absence of a large enough quantity of consistent, high-MW raw polymer, and indeed, until now, there is no US raw supply of this polymer at all. While chitin and chitosan research has blossomed in Asia in the past 20 years, the companies producing chitin and chitosan materials, suffer from a known inconsistency in its purity and quality (i.e., DA and MW). More importantly, many materials described in this review cannot be prepared from this type of commercially available chitin. We would also note that the process for producing chitin today is multi-step, chemical and energy intensive; in other words, a fairly dirty process.33,113,114 Without a large and consistent supply of the new, high MW “extracted” chitin, the commercialization of materials that require this type of chitin will be severely constrained. Many new high value chitin materials, for example, those used in medical applications, can be 27 ACS Paragon Plus Environment


Page 28 of 44

developed using the unique properties of the extracted chitin, however, commercialization will require a consistent supply and high quality, purity, and MW. This review has noted examples of materials, such as thin films and electrospun mats, that cannot be obtained from commercial chitin,72-74,76 due to the extent of deacetylation and depolymerization which occurs in the current chitin pulping processes. This is slowly changing - starting in 2016, Mari Signum Mid-Atlantic, LLC115 has been designing and is building a chitin production plant in Richmond, VA using microwave-assisted extraction of the polymer from crustacean biomass with the help of [C2mim][OAc] IL. However, even this plant when commissioned will not be able to satisfy all the needs of the supply. The second challenge is that decades of working with plastic and producing materials from plastic, resulted in many producers being economically unable to change from their existing supply of raw synthetic polymers, as this means changing equipment, processing technologies, and other production resources and capabilities. Besides, such innovations usually require large initial investments, and the increased cost compared to current practice, especially during the early years, prohibits new entries. One more challenge is chitin quality. The polymer coming from the pulping of crustacean shells conducted outside of the US not only lacks important product specifications, but differs in properties depending on supplier and/or manufacturing process. Government regulations must however be implemented prior to commercialization of chitin-based products. First, chitin needs to be fully characterized including parameters such as its molecular weight, degree of deacetylation, and purity (absence of minerals, proteins and endotoxin content). Secondly, biodegradability of each material with indication of degradation time and conditions must be demonstrated. This is all in addition to demonstrating material suitability for a given purpose through efficacy testing (i.e., cytotoxicity, wound healing studies (if important), cell adhesion, 28 ACS Paragon Plus Environment

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cell proliferation). When advancing into product development, medical grade requirements (i.e., good manufacturing practice production lines) are also essential. The last remaining challenge is that chitin–based products are currently of significantly higher costs when compared to traditional synthetic plastic-based products, and this is why building businesses around this unique opportunity should start with high-value, medical market materials, that have been covered in this review. Today, biopolymers finally have started gaining recognition in multiple industrial sectors, when laws around environment protection are being enforced worldwide, and public environmental awareness has increased globally. Of course, biopolymers won’t replace plastics all at once, because of how cheap plastics are and how far we have come in our ability to find inventive uses for them. However, high-cost, high-value medical devices and implantables of chitin would more than cover the cost of its isolation, and with more of these high-value chitin-based products, we will reach a price point where all of a sudden, the other chitin-based manufactured goods will become more financially attractive. Economy comes with scale and there is no inherent reason the price could not drop. Maybe this is the time to start?

NOTES Dr. Robin D. Rogers is a named inventor on related patents and applications and has partial ownership of 525 Solutions, Inc., and Mari Signum Mid-Atlantic, LLC. Dr. Julia L. Shamshina is an inventor on related patents and applications, former employee of 525 Solutions, Inc, and current employee of Mari Signum Mid-Atlantic, LLC.

Julia L. Shamshina Dr. Julia L. Shamshina is a CTO of Mari Signum Mid-Atlantic, LLC. After gaining relevant experience during her PhD (2008) and postdoctoral studies at The University of Alabama, Dr. 29 ACS Paragon Plus Environment


Page 30 of 44

Shamshina joined Streamline Automation, LLC (Huntsville, AL) in 2010, where she was working on commercialization of advanced technologies for the aerospace and defense markets, supported by US Air Force, Army, and NASA. She’s a recipient of NASA Tech Brief Award for her work on hydrazine replacement with energetic ionic liquids (2011). In 2012, Dr. Shamshina joined the start-up company 525 Solutions, Inc., as a CTO, where she gained experience in developing a company’s technological backbone ‘from ground up’ providing technical leadership and ensuring the implementation of technological solutions. In 2016 – 2017, Dr. Shamshina was employed by McGill University as an Academic Associate in Green Chemistry, in the Department of Chemistry, Faculty of Science. She was responsible for both internal and service-oriented research, from biopolymers isolation to the production of materials with specific characteristics. In August 2017, Dr. Shamshina accepted Mari Signum Mid-Atlantic, LLC’s CTO position, where she implements a research and development policies, objectives, and initiatives. In 2018, as a part Mari Signum Mid-Atlantic, LLC, she was awarded the American Chemical Society Green Chemistry Challenge Award Focus Area 2, Greener Reaction Conditions for “A Practical Way to Mass Production of Chitin: The Only Facility in the U. S. to Use Ionic Liquid-Based Isolation Process”. She has published over 60 papers, 9 book chapters, and is a holder of 16 patents and patent applications. Dr. Shamshina’s research interests focus on all aspects of ionic liquids and biopolymer processing. She is particularly interested in potential industrial uses of chitin biopolymer and its utilization in preparation of high value materials, perusing the concept for elimination of synthetic plastics.


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Page 32 of 44

Robin D. Rogers Dr. Robin D. Rogers is President, Owner, and Founder of 525 Solutions, Inc., in Tuscaloosa, AL USA and a Research Professor at The University of Alabama. He obtained both his B.S. in Chemistry (1978, Summa Cum Laude) and his Ph.D. in Chemistry (1982) at The University of Alabama before starting his professorial career at Northern Illinois University in DeKalb, IL where he rose through the ranks to become Presidential Research Professor. In 1996, he returned to UA as a Professor where he held various titles including Director of the Center for Green Manufacturing (1998-2014), Distinguished Research Professor (2004-2014), and Robert Ramsay Chair of Chemistry (2005-2014). In 2007, he was also Chair of Green Chemistry and Co-Director of QUILL at The Queen’s University of Belfast in Northern Ireland (UK) before returning full time to UA from 2009-2014. Since 2009, he has been an Honorary Professor at the Chinese Academy of Sciences Institute for Process Engineering in Beijing, China. In 2015, he became Canada Excellence Research Chair in Green Chemistry and Green Chemicals at McGill University in Montreal, QC, Canada, where he remained until 2017, when he returned full time to the start-up company he founded in 2004 to accelerate the introduction of academic advances in sustainable development directly to Society. In 2019 he also served as Tage Erlander Professor at Stockholm University to help bring sustainable development to Sweden. Rogers holds 30 issued patents (plus numerous foreign equivalents) of which 15 are licensed and has published over 820 papers on a diverse array of topics. His research interests cover the use of ionic liquids and Green Chemistry for sustainable technology through innovation.


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Page 34 of 44

Dr. Paula Berton Dr. Paula Berton is Research Associate in Prof. Steven L. Bryant’s group at the University of Calgary and Chief Scientific Officer of CalAgua Innovations Corp. She received her Ph.D. degree in Chemistry in 2013, at the Universidad Nacional de San Luis, Argentina. Her research focuses on the use of Ionic Liquids as a basis for the design of sustainable and efficient separation and purification processes, with applicability in the areas of biomass and oil sectors. This resulted in more than 35 publications in scientific journals, over 1,300 citations, and an hindex of 19.

References


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1 2

3

4 5 6 7 8

9 10

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Synopsis: Compelling collection of examples of techniques utilized to process chitin and to prepare chitin-based functional materials: fibers, films, beads, and hydrogels



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Advances in Functional Chitin Materials: A Review - ACS Sustainable

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