Preparation and properties of high performance gelatin-based hydrogels with chitosan or hydroxyethyl cellulose for tissue engineering applications

ABSTRACT High performance gelatin-based biocompatible hybrid hydrogels are developed using functionalized polyethylene glycol as a cross-linker in presence of chitosan or hydroxyethyl cellulose. Tensile test shows robust and tunable mechanical properties and reveals non-linear and J-shaped stress-strain curves similar to those found for native extracellular matrix. Degradation study demonstrates that the mass loss and change in mechanical properties are dependent on hydrogel composition and cross-linking density. Structural features of the hydrogels are confirmed by infrared spectroscopy. A preliminary biological evaluation is carried out using rat myoblasts and human fibroblasts cell lines. The results show that all hydrogels allow cell adhesion and proliferation during four days culture, hence, they might have a great potential for use in the biomedical applications. GRAPHICAL ABSTRACT

[1]  R. Reis,et al.  Surface phosphorylation of chitosan significantly improves osteoblast cell viability, attachment and proliferation , 2010 .

[2]  Anuj Kumar,et al.  Fabrication, characterization and in vitro biocompatibility of electrospun hydroxyethyl cellulose/poly (vinyl) alcohol nanofibrous composite biomaterial for bone tissue engineering , 2016 .

[3]  P. K. Sehgal,et al.  Synthesis and Characterization of Hybrid Biodegradable Films From Bovine Hide Collagen and Cellulose Derivatives for Biomedical Applications , 2013 .

[4]  A. Bakry,et al.  Flexible aliphatic poly(isocyanurate–oxazolidone) resins based on poly(ethylene glycol) diglycidyl ether and 4,4′‐methylene dicyclohexyl diisocyanate , 2016 .

[5]  T. Caykara,et al.  Thermal behavior and network structure of poly(N-vinyl-2-pyrrolidone-crotonic acid) hydrogels prepared by radiation-induced polymerization , 2004 .

[6]  Alina Sionkowska,et al.  Current research on the blends of natural and synthetic polymers as new biomaterials: Review , 2011 .

[7]  D. Discher,et al.  Cell responses to the mechanochemical microenvironment--implications for regenerative medicine and drug delivery. , 2007, Advanced drug delivery reviews.

[8]  J. Bagu,et al.  Comparison of hexamethyldisilazane (HMDS), Peldri II, and critical‐point drying methods for scanning electron microscopy of biological specimens , 1993, Microscopy research and technique.

[9]  F. Abbasi,et al.  Microstructure and characteristic properties of gelatin/chitosan scaffold prepared by a combined freeze-drying/leaching method. , 2013, Materials science & engineering. C, Materials for biological applications.

[10]  João Rodrigues,et al.  Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. , 2012, Chemical Society reviews.

[11]  James C. Weaver,et al.  Hydrogels with tunable stress relaxation regulate stem cell fate and activity , 2015, Nature materials.

[12]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[13]  Jos Malda,et al.  Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair. , 2016, Trends in biotechnology.

[14]  A. Khademhosseini,et al.  Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology , 2006 .

[15]  K. Anseth,et al.  Hydrogel Cell Cultures , 2007, Science.

[16]  C. Tsvetanov,et al.  Hydrogels based on u.v.-crosslinked poly(ethylene oxide) – matrices for immobilization of Candida boidinii cells for xylitol production , 2008 .

[17]  H. Sung,et al.  Studies on epoxy compound fixation. , 1996, Journal of biomedical materials research.

[18]  Fabio Bignotti,et al.  Green composites and blends from leather industry waste , 2016 .

[19]  Ali Khademhosseini,et al.  Synthesis and characterization of tunable poly(ethylene glycol): gelatin methacrylate composite hydrogels. , 2011, Tissue engineering. Part A.

[20]  Ali Khademhosseini,et al.  Bioinspired materials for controlling stem cell fate. , 2010, Accounts of chemical research.

[21]  C. Bowman,et al.  Mechanical properties of hydrogels and their experimental determination. , 1996, Biomaterials.

[22]  Chaenyung Cha,et al.  25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine , 2014, Advanced materials.

[23]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[24]  M. Lazzari,et al.  Preparation and characterization of crosslinked chitosan/gelatin scaffolds by ice segregation induced self-assembly. , 2016, Carbohydrate polymers.

[25]  M. Oyen,et al.  Mechanical characterisation of hydrogel materials , 2014 .

[26]  M. Mohammadi,et al.  Different tyrosine autophosphorylation requirements in fibroblast growth factor receptor-1 mediate urokinase-type plasminogen activator induction and mitogenesis. , 1999, Molecular biology of the cell.

[27]  D. J. Montgomery,et al.  The physics of rubber elasticity , 1949 .

[28]  D. Seliktar Designing Cell-Compatible Hydrogels for Biomedical Applications , 2012, Science.

[29]  M. Ribeiro,et al.  Synthesis and characterization of a photocrosslinkable chitosan–gelatin hydrogel aimed for tissue regeneration , 2015 .