Abstract
Regenerative medicine represents an emerging multidisciplinary field that brings together engineering methods and complexity of life sciences into a unified fundamental understanding of structure-property relationship in micro/nano environment to develop the next generation of scaffolds and hydrogels to restore or improve tissue functions. Chitosan has several unique physico-chemical properties that make it a highly desirable polysaccharide for various applications such as, biomedical, food, nutraceutical, agriculture, packaging, coating, etc. However, the utilization of chitosan in regenerative medicine is often limited due to its inadequate mechanical, barrier and thermal properties. Cellulosic nanomaterials (CNs), owing to their exceptional mechanical strength, ease of chemical modification, biocompatibility and favorable interaction with chitosan, represent an attractive candidate for the fabrication of chitosan/ CNs scaffolds and hydrogels. The unique mechanical and biological properties of the chitosan/CNs bio-nanocomposite make them a material of choice for the development of next generation bio-scaffolds and hydrogels for regenerative medicine applications. In this review, we have summarized the preparation method, mechanical properties, morphology, cytotoxicity/ biocompatibility of chitosan/CNs nanocomposites for regenerative medicine applications, which comprises tissue engineering and wound dressing applications.
Keywords: Cellulose, nanomaterials, morphology, cytotoxicity, biomedical application, polysaccharide.
[1]
Sainitya, R.; Sriram, M.; Kalyanaraman, V.; Dhivya, S.; Saravanan, S.; Vairamani, M.; Sastry, T.P.; Selvamurugan, N. Scaffolds containing chitosan/carboxymethyl cellulose/mesoporous wollastonite for bone tissue engineering. Int. J. Biol. Macromol., 2015, 80, 481-488.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.07.016] [PMID: 26188305]
[http://dx.doi.org/10.1016/j.ijbiomac.2015.07.016] [PMID: 26188305]
[2]
Rhim, J-W. Effect of clay contents on mechanical and water vapor barrier properties of agar-based nanocomposite films. Carbohydr. Polym., 2011, 86(2), 691-699.
[http://dx.doi.org/10.1016/j.carbpol.2011.05.010]
[http://dx.doi.org/10.1016/j.carbpol.2011.05.010]
[3]
Khan, A.; Vu, K.D.; Chauve, G.; Bouchard, J.; Riedl, B.; Lacroix, M. Optimization of microfluidization for the homogeneous distribution of cellulose nanocrystals (CNCs) in biopolymeric matrix. Cellulose, 2014, 21(5), 3457-3468.
[http://dx.doi.org/10.1007/s10570-014-0361-9]
[http://dx.doi.org/10.1007/s10570-014-0361-9]
[4]
Kim, J.; Cai, Z.; Chen, Y. Biocompatible bacterial cellulose composites for biomedical application. J. Nanotechnol. Eng. Med., 2010, 1(1) 011006
[http://dx.doi.org/10.1115/1.4000062]
[http://dx.doi.org/10.1115/1.4000062]
[5]
Croisier, F.; Jérôme, C. Chitosan-based biomaterials for tissue engineering. Eur. Polym. J., 2013, 49(4), 780-792.
[http://dx.doi.org/10.1016/j.eurpolymj.2012.12.009]
[http://dx.doi.org/10.1016/j.eurpolymj.2012.12.009]
[6]
Rhim, J-W.; Hong, S-I.; Park, H-M.; Ng, P.K.W. Preparation and characterization of chitosan-based nanocomposite films with antimicrobial activity. J. Agric. Food Chem., 2006, 54(16), 5814-5822.
[http://dx.doi.org/10.1021/jf060658h] [PMID: 16881682]
[http://dx.doi.org/10.1021/jf060658h] [PMID: 16881682]
[7]
Khan, A.; Khan, R.A.; Salmieri, S.; Le Tien, C.; Riedl, B.; Bouchard, J.; Chauve, G.; Tan, V.; Kamal, M.R.; Lacroix, M. Mechanical and barrier properties of nanocrystalline cellulose reinforced chitosan based nanocomposite films. Carbohydr. Polym., 2012, 90(4), 1601-1608.
[http://dx.doi.org/10.1016/j.carbpol.2012.07.037] [PMID: 22944422]
[http://dx.doi.org/10.1016/j.carbpol.2012.07.037] [PMID: 22944422]
[8]
Ling, S.; Chen, W.; Fan, Y.; Zheng, K.; Jin, K.; Yu, H.; Buehler, M.J.; Kaplan, D.L. Biopolymer nanofibrils: structure, modeling, preparation, and applications. Prog. Polym. Sci., 2018, 85, 1-56.
[http://dx.doi.org/10.1016/j.progpolymsci.2018.06.004] [PMID: 31915410]
[http://dx.doi.org/10.1016/j.progpolymsci.2018.06.004] [PMID: 31915410]
[9]
Gao, J.; Li, Q.; Chen, W.; Liu, Y.; Yu, H. Self-assembly of nanocellulose and indomethacin into hierarchically ordered structures with high encapsulation efficiency for sustained release applications. ChemPlusChem, 2014, 79(5), 725-731.
[http://dx.doi.org/10.1002/cplu.201300434]
[http://dx.doi.org/10.1002/cplu.201300434]
[10]
Grishkewich, N.; Mohammed, N.; Tang, J.; Tam, K.C. Recent advances in the application of cellulose nanocrystals. Curr. Opin. Colloid Interface Sci., 2017, 29, 32-45.
[http://dx.doi.org/10.1016/j.cocis.2017.01.005]
[http://dx.doi.org/10.1016/j.cocis.2017.01.005]
[11]
Khan, A.; Wen, Y.; Huq, T.; Ni, Y. Cellulosic nanomaterials in food and nutraceutical applications: a review. J. Agric. Food Chem., 2018, 66(1), 8-19.
[http://dx.doi.org/10.1021/acs.jafc.7b04204] [PMID: 29251504]
[http://dx.doi.org/10.1021/acs.jafc.7b04204] [PMID: 29251504]
[12]
Dai, L.; Cheng, T.; Duan, C.; Zhao, W.; Zhang, W.; Zou, X.; Aspler, J.; Ni, Y. 3D printing using plant-derived cellulose and its derivatives: A review. Carbohydr. Polym., 2019, 203, 71-86.
[http://dx.doi.org/10.1016/j.carbpol.2018.09.027] [PMID: 30318237]
[http://dx.doi.org/10.1016/j.carbpol.2018.09.027] [PMID: 30318237]
[13]
Elazzouzi-Hafraoui, S.; Nishiyama, Y.; Putaux, J.L.; Heux, L.; Dubreuil, F.; Rochas, C. The shape and size distribution of crystalline nanoparticles prepared by acid hydrolysis of native cellulose. Biomacromolecules, 2008, 9(1), 57-65.
[http://dx.doi.org/10.1021/bm700769p] [PMID: 18052127]
[http://dx.doi.org/10.1021/bm700769p] [PMID: 18052127]
[14]
Li, X.; Liu, Y.; Yu, Y.; Chen, W.; Liu, Y.; Yu, H. Nanoformulations of quercetin and cellulose nanofibers as healthcare supplements with sustained antioxidant activity. Carbohydr. Polym., 2019, 207, 160-168.
[http://dx.doi.org/10.1016/j.carbpol.2018.11.084] [PMID: 30599995]
[http://dx.doi.org/10.1016/j.carbpol.2018.11.084] [PMID: 30599995]
[15]
Azarniya, A.; Eslahi, N.; Mahmoudi, N.; Simchi, A. Effect of graphene oxide nanosheets on the physico-mechanical properties of chitosan/bacterial cellulose nanofibrous composites. Compos., Part A Appl. Sci. Manuf., 2016, 85, 113-122.
[http://dx.doi.org/10.1016/j.compositesa.2016.03.011]
[http://dx.doi.org/10.1016/j.compositesa.2016.03.011]
[16]
He, J.X.; Tan, W.L.; Han, Q.M.; Cui, S.Z.; Shao, W.; Sang, F. Fabrication of silk fibroin/cellulose whiskers-chitosan composite porous scaffolds by layer-by-layer assembly for application in bone tissue engineering. J. Mater. Sci., 2016, 51(9), 4399-4410.
[http://dx.doi.org/10.1007/s10853-016-9752-7]
[http://dx.doi.org/10.1007/s10853-016-9752-7]
[17]
Wang, Y.; Uetani, K.; Liu, S.; Zhang, X.; Wang, Y.; Lu, P.; Wei, T.; Fan, Z.; Shen, J.; Yu, H. Multifunctional bionanocomposite foams with a chitosan matrix reinforced by nanofibrillated cellulose. ChemNanoMat, 2017, 3(2), 98-108.
[http://dx.doi.org/10.1002/cnma.201600266]
[http://dx.doi.org/10.1002/cnma.201600266]
[18]
Ko, S.W.; Soriano, J.P.E.; Lee, J.Y.; Unnithan, A.R.; Park, C.H.; Kim, C.S. Nature derived scaffolds for tissue engineering applications: Design and fabrication of a composite scaffold incorporating chitosan-g-d,l-lactic acid and cellulose nanocrystals from Lactuca sativa L. cv green leaf. Int. J. Biol. Macromol., 2018, 110, 504-513.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.10.109] [PMID: 29054519]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.10.109] [PMID: 29054519]
[19]
Sampath, U.G.T.M.; Ching, Y.C.; Chuah, C.H.; Singh, R.; Lin, P.C. Preparation and characterization of nanocellulose reinforced semi-interpenetrating polymer network of chitosan hydrogel. Cellulose, 2017, 24(5), 2215-2228.
[http://dx.doi.org/10.1007/s10570-017-1251-8]
[http://dx.doi.org/10.1007/s10570-017-1251-8]
[20]
Du, H.; Liu, W.; Zhang, M.; Si, C.; Zhang, X.; Li, B. Cellulose nanocrystals and cellulose nanofibrils based hydrogels for biomedical applications. Carbohydr. Polym., 2019, 209, 130-144.
[http://dx.doi.org/10.1016/j.carbpol.2019.01.020] [PMID: 30732792]
[http://dx.doi.org/10.1016/j.carbpol.2019.01.020] [PMID: 30732792]
[21]
Fu, L-H.; Qi, C.; Ma, M-G.; Wan, P. Multifunctional cellulose-based hydrogels for biomedical applications. J. Mater. Chem. B Mater. Biol. Med., 2019, 7(10), 1541-1562.
[http://dx.doi.org/10.1039/C8TB02331J] [PMID: 32254901]
[http://dx.doi.org/10.1039/C8TB02331J] [PMID: 32254901]
[22]
Anitha, A.; Sowmya, S.; Kumar, P.T.S.; Deepthi, S.; Chennazhi, K.P.; Ehrlich, H.; Tsurkan, M.; Jayakumar, R. Chitin and chitosan in selected biomedical applications. Prog. Polym. Sci., 2014, 39(9), 1644-1667.
[http://dx.doi.org/10.1016/j.progpolymsci.2014.02.008]
[http://dx.doi.org/10.1016/j.progpolymsci.2014.02.008]
[23]
Shahabipour, F.; Banach, M.; Johnston, T.P.; Pirro, M.; Sahebkar, A. Novel approaches toward the generation of bioscaffolds as a potential therapy in cardiovascular tissue engineering. Int. J. Cardiol., 2017, 228, 319-326.
[http://dx.doi.org/10.1016/j.ijcard.2016.11.210] [PMID: 27866022]
[http://dx.doi.org/10.1016/j.ijcard.2016.11.210] [PMID: 27866022]
[24]
Adekogbe, I.; Ghanem, A. Fabrication and characterization of DTBP-crosslinked chitosan scaffolds for skin tissue engineering. Biomaterials, 2005, 26(35), 7241-7250.
[http://dx.doi.org/10.1016/j.biomaterials.2005.05.043] [PMID: 16011846]
[http://dx.doi.org/10.1016/j.biomaterials.2005.05.043] [PMID: 16011846]
[25]
Ma, L.; Gao, C.; Mao, Z.; Zhou, J.; Shen, J.; Hu, X.; Han, C. Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering. Biomaterials, 2003, 24(26), 4833-4841.
[http://dx.doi.org/10.1016/S0142-9612(03)00374-0] [PMID: 14530080]
[http://dx.doi.org/10.1016/S0142-9612(03)00374-0] [PMID: 14530080]
[26]
Freyman, T.M.; Yannas, I.V.; Gibson, L.J. Cellular materials as porous scaffolds for tissue engineering. Prog. Mater. Sci., 2001, 46(3-4), 273-282.
[http://dx.doi.org/10.1016/S0079-6425(00)00018-9]
[http://dx.doi.org/10.1016/S0079-6425(00)00018-9]
[27]
Kanimozhi, K.; Khaleel Basha, S.; Sugantha Kumari, V.; Kaviyarasu, K.; Maaza, M. In vitro cytocompatibility of chitosan/PVA/methylcellulose - Nanocellulose nanocomposites scaffolds using L929 fibroblast cells. Appl. Surf. Sci., 2018, 449, 574-583.
[http://dx.doi.org/10.1016/j.apsusc.2017.11.197]
[http://dx.doi.org/10.1016/j.apsusc.2017.11.197]
[28]
Kawasaki, T.; Nakaji-Hirabayashi, T.; Masuyama, K.; Fujita, S.; Kitano, H. Complex film of chitosan and carboxymethyl cellulose nanofibers. Colloids Surf. B Biointerfaces, 2016, 139, 95-99.
[http://dx.doi.org/10.1016/j.colsurfb.2015.11.056] [PMID: 26700238]
[http://dx.doi.org/10.1016/j.colsurfb.2015.11.056] [PMID: 26700238]
[29]
Li, Z.; Ramay, H.R.; Hauch, K.D.; Xiao, D.; Zhang, M. Chitosan-alginate hybrid scaffolds for bone tissue engineering. Biomaterials, 2005, 26(18), 3919-3928.
[http://dx.doi.org/10.1016/j.biomaterials.2004.09.062] [PMID: 15626439]
[http://dx.doi.org/10.1016/j.biomaterials.2004.09.062] [PMID: 15626439]
[30]
Li, G.; Nandgaonkar, A.G.; Habibi, Y.; Krause, W.E.; Wei, Q.; Lucia, L.A. An environmentally benign approach to achieving vectorial alignment and high microporosity in bacterial cellulose/chitosan scaffolds. RSC Advances, 2017, 7(23), 13678-13688.
[http://dx.doi.org/10.1039/C6RA26049G]
[http://dx.doi.org/10.1039/C6RA26049G]
[31]
Ridolfi, D.M.; Lemes, A.P.; de Oliveira, S.; Justo, G.Z.; Palladino, M.V.; Durán, N. Electrospun poly(ethylene oxide)/chitosan nanofibers with cellulose nanocrystals as support for cell culture of 3T3 fibroblasts. Cellulose, 2017, 24(8), 3353-3365.
[http://dx.doi.org/10.1007/s10570-017-1362-2]
[http://dx.doi.org/10.1007/s10570-017-1362-2]
[32]
Yan, H.; Chen, X.; Feng, M.; Shi, Z.; Zhang, D.; Lin, Q. Layer-by-layer assembly of 3D alginate-chitosan-gelatin composite scaffold incorporating bacterial cellulose nanocrystals for bone tissue engineering. Mater. Lett., 2017, 209, 492-496.
[http://dx.doi.org/10.1016/j.matlet.2017.08.093]
[http://dx.doi.org/10.1016/j.matlet.2017.08.093]
[33]
Lee, H.; Kim, G. Cryogenically fabricated three-dimensional chitosan scaffolds with pore size-controlled structures for biomedical applications. Carbohydr. Polym., 2011, 85(4), 817-823.
[http://dx.doi.org/10.1016/j.carbpol.2011.04.001]
[http://dx.doi.org/10.1016/j.carbpol.2011.04.001]
[34]
Pinho, E.; Soares, G. Functionalization of cotton cellulose for improved wound healing. J. Mater. Chem. B Mater. Biol. Med., 2018, 6(13), 1887-1898.
[http://dx.doi.org/10.1039/C8TB00052B] [PMID: 32254354]
[http://dx.doi.org/10.1039/C8TB00052B] [PMID: 32254354]
[35]
Fan, L.; Yang, H.; Yang, J.; Peng, M.; Hu, J. Preparation and characterization of chitosan/gelatin/PVA hydrogel for wound dressings. Carbohydr. Polym., 2016, 146, 427-434.
[http://dx.doi.org/10.1016/j.carbpol.2016.03.002] [PMID: 27112893]
[http://dx.doi.org/10.1016/j.carbpol.2016.03.002] [PMID: 27112893]
[36]
Czaja, W.K.; Young, D.J.; Kawecki, M.; Brown, R.M., Jr The future prospects of microbial cellulose in biomedical applications. Biomacromolecules, 2007, 8(1), 1-12.
[http://dx.doi.org/10.1021/bm060620d] [PMID: 17206781]
[http://dx.doi.org/10.1021/bm060620d] [PMID: 17206781]
[37]
Jayakumar, R.; Prabaharan, M.; Sudheesh Kumar, P.T.; Nair, S.V.; Tamura, H. Biomaterials based on chitin and chitosan in wound dressing applications. Biotechnol. Adv., 2011, 29(3), 322-337.
[http://dx.doi.org/10.1016/j.biotechadv.2011.01.005] [PMID: 21262336]
[http://dx.doi.org/10.1016/j.biotechadv.2011.01.005] [PMID: 21262336]
[38]
Poonguzhali, R.; Basha, S.K.; Kumari, V.S. Synthesis and characterization of chitosan-PVP-nanocellulose composites for in-vitro wound dressing application. Int. J. Biol. Macromol., 2017, 105(Pt 1), 111-120.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.07.006] [PMID: 28698076]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.07.006] [PMID: 28698076]
[39]
Haider, A.; Haider, S.; Kang, I.K.; Kumar, A.; Kummara, M.R.; Kamal, T.; Han, S.S. A novel use of cellulose based filter paper containing silver nanoparticles for its potential application as wound dressing agent. Int. J. Biol. Macromol., 2018, 108, 455-461.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.12.022] [PMID: 29222019]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.12.022] [PMID: 29222019]
[40]
Ardila, N.; Medina, N.; Arkoun, M.; Ajji, A.; Panchal, C.J. Chitosan - bacterial nanocellulose nanofibrous structures for potential wound dressing applications. Cellulose, 2016, 23(5), 3089-3104.
[http://dx.doi.org/10.1007/s10570-016-1022-y]
[http://dx.doi.org/10.1007/s10570-016-1022-y]
[41]
Jia, Y.; Wang, X.; Huo, M.; Zhai, X.; Li, F.; Zhong, C. Preparation and characterization of a novel bacterial cellulose/chitosan bio-hydrogel. Nanomater. Nanotechnol., 2017, 7, 1-8.
[http://dx.doi.org/10.1177/1847980417707172]
[http://dx.doi.org/10.1177/1847980417707172]
[42]
Nguyen, T.H.M.; Abueva, C.; Ho, H.V.; Lee, S.Y.; Lee, B.T. In vitro and in vivo acute response towards injectable thermosensitive chitosan/TEMPO-oxidized cellulose nanofiber hydrogel. Carbohydr. Polym., 2018, 180, 246-255.
[http://dx.doi.org/10.1016/j.carbpol.2017.10.032] [PMID: 29103503]
[http://dx.doi.org/10.1016/j.carbpol.2017.10.032] [PMID: 29103503]
[43]
Khan, A.; Salmieri, S.; Fraschini, C.; Bouchard, J.; Riedl, B.; Lacroix, M. Genipin cross-linked nanocomposite films for the immobilization of antimicrobial agent. ACS Appl. Mater. Interfaces, 2014, 6(17), 15232-15242.
[http://dx.doi.org/10.1021/am503564m] [PMID: 25140839]
[http://dx.doi.org/10.1021/am503564m] [PMID: 25140839]
[44]
Ciechanska, D. Multifunctional bacterial cellulose/chitosan composite materials for medical applications. Fibres Text. East. Eur., 2004, 12(4), 69-72.
[45]
Zhang, P.; Chen, L.; Zhang, Q.; Hong, F.F. Using in situ dynamic cultures to rapidly biofabricate fabric-reinforced composites of chitosan/bacterial nanocellulose for antibacterial wound dressings. Front. Microbiol., 2016, 7, 260.
[http://dx.doi.org/10.3389/fmicb.2016.00260] [PMID: 26973634]
[http://dx.doi.org/10.3389/fmicb.2016.00260] [PMID: 26973634]
Related Journals
Current Pharmaceutical Design
Current Topics in Medicinal Chemistry
Current Respiratory Medicine Reviews
Infectious Disorders - Drug Targets
Endocrine, Metabolic & Immune Disorders - Drug Targets
Anti-Infective Agents
Coronaviruses
Recent Advances in Inflammation & Allergy Drug Discovery
Current Probiotics
Article Metrics
21
3