Preparation and in vitro cytocompatibility of chitosan-siloxane hybrid hydrogels.

Injectable systems can be used in minimally invasive surgical applications. Although chitosan-glycerophosphate hydrogel systems are biodegradable and biocompatible, the long periods of time required for their effective gelation have severely limited their clinical application. The challenges currently facing researchers in this field are therefore focused on shortening the gelation time and biocompatibility of these materials to develop hydrogels suitable for clinical application. Chitosan and γ-glycidoxypropyltrimethoxysilane (GPTMS) hybrids have recently demonstrated good cytocompatibility with respect to human osteoblastic cells (MG63) and human bone marrow cells. Although these precursor sols could form gels under physiological conditions, they required neutralization with a sodium hydroxide solution. In this study, the chitosan-GPTMS hybrid systems were neutralized with glycerophosphate to prepare injectable hydrogels. The results revealed that the gelation time of the hydrogels could be controlled by the amount of GPTMS in the precursor sols. The in vitro cytocompatibility of the hydrogels were evaluated in terms of the proliferation of MG63 cells cultured either directly onto the hydrogels or indirectly onto the cell culture plate under a hydrogel insert. In the former case, the cells showed good attachment and proliferated for up to 7 days. Similar results were observed in the in direct culture. These results suggest that this new chitosan-GPTMS hydrogel could potentially be used as an injectable biomaterial in clinical applications.

[1]  S. Hayakawa,et al.  In V itro Bioactivity and MG63 Cytocompatibility of Chitosan-Silicate Hybrids , 2013 .

[2]  M. Shive,et al.  Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects. , 2005, The Journal of bone and joint surgery. American volume.

[3]  J. Polak,et al.  Enhanced derivation of osteogenic cells from murine embryonic stem cells after treatment with ionic dissolution products of 58S bioactive sol-gel glass. , 2005, Tissue engineering.

[4]  S. Hirano,et al.  Structure of insect chitin isolated from beetle larva cuticle and silkworm (Bombyx mori) pupa exuvia. , 2000, International journal of biological macromolecules.

[5]  J. D. de Bruijn,et al.  Biocompatibility and gelation of chitosan-glycerol phosphate hydrogels. , 2008, Journal of biomedical materials research. Part A.

[6]  J. Sun,et al.  Chitosan-glycerol phosphate/blood implants increase cell recruitment, transient vascularization and subchondral bone remodeling in drilled cartilage defects. , 2007, Osteoarthritis and cartilage.

[7]  Julian R. Jones,et al.  Nodule formation and mineralisation of human primary osteoblasts cultured on a porous bioactive glass scaffold. , 2004, Biomaterials.

[8]  Yuki Shirosaki,et al.  Synthesis and characterization of chitosan-silicate hydrogel as resorbable vehicle for bonelike-bone graft. , 2009, Journal of nanoscience and nanotechnology.

[9]  P. Carreau,et al.  Physical gelation of chitosan in the presence of beta-glycerophosphate: the effect of temperature. , 2005, Biomacromolecules.

[10]  J. Leroux,et al.  Novel injectable neutral solutions of chitosan form biodegradable gels in situ. , 2000, Biomaterials.

[11]  M. Rinaudo,et al.  Preparation and characterization of fully deacetylated chitosan , 1983 .

[12]  M. McKee,et al.  Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondral bone in microdrilled rabbit defects. , 2007, Osteoarthritis and cartilage.

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

[14]  T. Chandy,et al.  Chitosan--as a biomaterial. , 1990, Biomaterials, artificial cells, and artificial organs.

[15]  Kanji Tsuru,et al.  Physical, chemical and in vitro biological profile of chitosan hybrid membrane as a function of organosiloxane concentration. , 2009, Acta biomaterialia.

[16]  A. Atkinson,et al.  Formation of silica/epoxy hybrid network polymers , 2003 .

[17]  A Hatefi,et al.  Biodegradable injectable in situ forming drug delivery systems. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[18]  M D McKee,et al.  Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. , 2005, Osteoarthritis and cartilage.

[19]  M. Berridge,et al.  Characterization of the cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT): subcellular localization, substrate dependence, and involvement of mitochondrial electron transport in MTT reduction. , 1993, Archives of biochemistry and biophysics.

[20]  L L Hench,et al.  Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass 45S5 dissolution. , 2001, Journal of biomedical materials research.

[21]  A. Mikos,et al.  Injectable biodegradable materials for orthopedic tissue engineering. , 2000, Biomaterials.

[22]  Kanji Tsuru,et al.  Synthesis and cytocompatibility of porous chitosan–silicate hybrids for tissue engineering scaffold application , 2008 .

[23]  J. Sun,et al.  Cytocompatible gel formation of chitosan-glycerol phosphate solutions supplemented with hydroxyl ethyl cellulose is due to the presence of glyoxal. , 2007, Journal of biomedical materials research. Part A.

[24]  Julian R. Jones,et al.  Epoxide opening versus silica condensation during sol-gel hybrid biomaterial synthesis. , 2013, Chemistry.

[25]  Kanji Tsuru,et al.  In vitro cytocompatibility of MG63 cells on chitosan-organosiloxane hybrid membranes. , 2005, Biomaterials.

[26]  Glenn D Prestwich,et al.  In situ crosslinkable hyaluronan hydrogels for tissue engineering. , 2004, Biomaterials.

[27]  Larry L. Hench,et al.  Bioglass ®45S5 Stimulates Osteoblast Turnover and Enhances Bone Formation In Vitro: Implications and Applications for Bone Tissue Engineering , 2000, Calcified Tissue International.

[28]  K. Vårum,et al.  Quantitative determination of chitosans by ninhydrin , 1999 .

[29]  Larry L. Hench,et al.  Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass t 45 S 5 dissolution , 2000 .

[30]  M. Zhang,et al.  ^ C CP/MAS NMR Spectral Analysis of 6-O-Tosyl, 6-Deoxy-6-iodo, and 6-Deoxy Derivatives of N-Acetylchitosan in a Solid State , 1994 .

[31]  I. Gibson,et al.  Preparation of osteocompatible Si(IV)-enriched chitosan-silicate hybrids , 2010 .