Abstract
Chitinous nanofibers (NFs) exhibit a specific physiological activity not observed in the powdered form. While three-dimensional cell culture scaffolds are being actively studied, attempts have been made to use chitinous materials as well. In this study, we aimed to develop a cell-adhesive chitinous NF-based flexible hydrogel. Such a gel will be easy to handle, and there is a possibility that the gel will be able to be three-dimensionally molded. For this purpose, the surface of chitinous NFs was modified to introduce vinyl polymerizable functional groups, and the modified NFs were copolymerized with an N-isopropylacrylamide (NIPAM) monomer in an aqueous system. First, by modification of chitosan NFs with maleic anhydride (MA), a flexible gel was obtained by subsequent copolymerization with NIPAM. However, the adhesion of L929 mouse fibroblasts onto MA-modified NFs was extremely lower than that of chitosan NFs, probably due to the simultaneous introduction of anionic groups. The desired cell-adhesive flexible hydrogel was eventually obtained by introducing cationic groups and polymerizable functional groups on the chitinous NF surface. Cells adhered to the gel could be detached by cooling to 4 °C. The composite hydrogel fabricated here may be useful as a cell culture scaffold material in regenerative medicine.
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References
Ifuku S, Saimoto H. Chitin nanofibers: preparations, modifications, and applications. Nanoscale. 2012;4:3308–18.
Abe K, Iwamoto S, Yano H. Obtaining cellulose nanofibers with a uniform width of 15 nm from wood. Biomacromolecules. 2007;8:3276–8.
Isogai A, Saito T, Fukuzumi H. TEMPO-oxidized cellulose nanofibers. Nanoscale. 2011;3:71–85.
Azuma K, Ifuku S, Osaki T, Okamoto Y, Minami S. Preparation and biomedical applications of chitin and chitosan nanofibers. J Biomed Nanotechnol. 2014;10:2891–920.
Azuma K, Osaki T, Wakuda T, Ifuku S, Saimoto H, Tsuka T, et al. Beneficial and preventive effect of chitin nanofibrils in a dextran sulfate sodium-induced acute ulcerative colitis model. Carbohydr Polym. 2012;87:1399–403.
Izumi R, Komada S, Ochi K, Karasawa L, Osaki T, Murahata Y, et al. Favorable effects of superficially deacetylated chitin nanofibrils on the wound healing process. Carbohydr Polym. 2015;123:461–7.
Tabuchi R, Azuma K, Izumi R, Tanou T, Okamoto Y, Nagae T, et al. Biomaterials based on freeze dried surface-deacetylated chitin nanofibers reinforced with sulfobutyl ether β-cyclodextrin gel in wound dressing applications. Int J Pharm. 2016;511:1080–7.
Maude S, Ingham E, Aggeli A. Biomimetic self-assembling peptides as scaffolds for soft tissue engineering. Nanomedicine. 2013;8:823–47.
Matson JB, Stupp SI. Self-assembling peptide scaffolds for regenerative medicine. Chem Commun. 2012;48:26–33.
Matsusaki M, Akashi M. Control of extracellular microenvironments using polymer/protein nanofilms for the development of three-dimensional human tissue chips. Polym J. 2014;46:524–36.
Li T, Liang Y, Wang Z, Zhang W, Wang L, Zhou Q, et al. Tissue-engineered scaffold based on carboxymethyl chitin or chitosan for corneal epithelial transplantation. Polym J. 2018;50:511–21.
Torres-Rendon JG, Femmer T, De Laporte L, Tigges T, Rahimi K, Gremse F, et al. Bioactive gyroid scaffolds formed by sacrificial templating of nanocellulose and nanochitin hydrogels as instructive platforms for biomimetic tissue engineering. Adv Mater. 2015;27:2989–95.
Suzuki S, Teramoto Y. Simple inkjet process to fabricate microstructures of chitinous nanocrystals for cell patterning. Biomacromolecules. 2017;16:1993–9.
Kobe R, Iwamoto S, Endo T, Yoshitani K, Teramoto Y. Stretchable composite hydrogels incorporating modified cellulose nanofiber with dispersibility and polymerizability: mechanical property control and nanofiber orientation. Polymer. 2016;97:480–6.
Okano T, Yamada N, Sakai H. A novel recoverv svstern for cultured cells using plasma-treated polystyrene dishes grafted with poly(N-isopropylacrylarnide). J Biomed Mater Res. 1993;27:1243–51.
Shimizu T, Yamato M, Kikuchi A, Okano T. Cell sheet engineering for myocardial tissue reconstruction. Biomaterials. 2003;24:2309–16.
Nishimura K, Ishihara C, Ukei S, Tokura S, Azuma I. Stimulation of cytokine production in mice using deacetylated chitin. Vaccine. 1986;4:151–6.
Minagawa T, Okamura Y, Shigemasa Y, Minami S, Okamoto Y. Effects of molecular weight and deacetylation degree of chitin/chitosan on wound healing. Carbohydr Polym. 2007;67:640–4.
Rwei SP, Chen YM, Lin WY, Chiang WY. Synthesis and rheological characterization of water-soluble glycidyltrimethylammonium-chitosan. Mar Drugs. 2014;12:5547–62.
Marsano E, De Paz L, Tambuscio E, Bianchi E. Cellulose methacrylate: synthesis and liquid crystalline behaviour of solutions and gels. Polymer. 1998;39:4289–94.
Fang Y, Zhang R, Duan B, Liu M, Lu A, Zhang L. Recyclable universal solvents for chitin to chitosan with various degrees of acetylation and construction of robust hydrogels. ACS Sustain Chem Eng. 2017;5:2725–33.
Altankov G, Richau K, Groth T. The role of surface zeta potential and substratum chemistry for regulation of dermal fibroblasts interaction. Materwiss Werksttech. 2003;34:1120–8.
Chang HY, Huang CC, Lin KY, Kao WL, Liao HY, You YW, et al. Effect of surface potential on NIH3T3 cell adhesion and proliferation. J Phys Chem C. 2014;118:14464–70.
Domsly JG, Roberts GAF. Evaluation of infrared spectroscopic techniques for analysing chitosan. Die Makromol Chem. 1985;186:1671–7.
Tong Y, Zhang Y, Liu Y, Cai H, Zhang W, Tan WS. POSS-enhanced thermosensitive hybrid hydrogels for cell adhesion and detachment. RSC Adv. 2018;8:13813–9.
Wang L, Lu G, Lu Q, Kaplan DL. Controlling cell behavior on silk nanofiber hydrogels with tunable anisotropic structures. ACS Biomater Sci Eng. 2018;4:933–41.
Acknowledgements
This work was partially financed by a Grant-in-Aid for Scientific Research (A) (No. 17H01480) from the Japan Society for the Promotion of Science and JST-Mirai Program (JPMJMI18E3) from the Japan Science and Technology Agency (JST).
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Goto, K., Teramoto, Y. Development of chitinous nanofiber-based flexible composite hydrogels capable of cell adhesion and detachment. Polym J 52, 959–967 (2020). https://doi.org/10.1038/s41428-020-0324-y
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DOI: https://doi.org/10.1038/s41428-020-0324-y