Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, People's Republic of China.
J Biomed Mater Res A. 2011 Nov;99(2):316-26. doi: 10.1002/jbm.a.33199. Epub 2011 Sep 1.
Novel injectable biodegradable glycol chitosan hydrogels were developed based on thiolated glycol chitosan (GC-SH) and water soluble oligo(acryloyl carbonate)-b-poly(ethylene glycol)-b-oligo(acryloyl carbonate) (OAC-PEG-OAC) triblock copolymers via Michael-type addition reaction. The rheology measurements showed that robust hydrogels were formed rapidly upon mixing aqueous solutions of GC-SH and OAC-PEG-OAC at remarkably low total polymer concentrations of 1.5-4.5 wt % under physiological conditions. The gelation times (varying from 10 s to 17 min) and storage moduli (100 to 4300 Pa) of hydrogels could be controlled by degrees of substitution (DS) of GC-SH, solution pH, and polymer concentration. These glycol chitosan hydrogels had microporous structures, low swelling and slow hydrolytic degradation (stable for over 6 months) under physiological conditions. Notably, these hydrogels were prone to enzymatic degradation with lysozyme. The multiple acryloyl functional groups of OAC-PEG-OAC allowed facile conjugation with thiol-containing biomolecules prior to gelation endowing hydrogels with specific bioactivity. The preliminary cell culture studies revealed that these glycol chitosan hydrogels were cell non-adhesive while Gly-Arg-Gly-Asp-Cys (GRGDC) peptide modified hydrogels could well support adhesion and growth of both MG63 osteoblast and L929 fibroblast cells. These rapidly in situ forming enzymatically biodegradable hybrid hydrogels have great potentials in the development of injectable cell-specific bioactive extracellular matrices for tissue engineering.
新型可注射生物可降解的乙二醇壳聚糖水凝胶是基于巯基化的乙二醇壳聚糖（GC-SH）和水溶性的寡（丙烯酰碳酸酯）-b-聚（乙二醇）-b-寡（丙烯酰碳酸酯）（OAC-PEG-OAC）三嵌段共聚物通过迈克尔加成反应开发的。流变学测量表明，在生理条件下，将 GC-SH 和 OAC-PEG-OAC 的水溶液以非常低的总聚合物浓度（1.5-4.5wt%）混合时，迅速形成坚固的水凝胶。水凝胶的凝胶时间（从 10s 到 17min 不等）和储能模量（100-4300Pa）可以通过 GC-SH 的取代度、溶液 pH 值和聚合物浓度来控制。这些乙二醇壳聚糖水凝胶具有微孔结构，在生理条件下具有低溶胀和缓慢的水解降解（稳定超过 6 个月）。值得注意的是，这些水凝胶易于被溶菌酶酶解。OAC-PEG-OAC 的多个丙烯酰基官能团允许在凝胶化之前与含巯基的生物分子进行方便的缀合，赋予水凝胶特定的生物活性。初步的细胞培养研究表明，这些乙二醇壳聚糖水凝胶对细胞无粘附性，而 Gly-Arg-Gly-Asp-Cys（GRGDC）肽修饰的水凝胶可以很好地支持 MG63 成骨细胞和 L929 成纤维细胞的粘附和生长。这些快速原位形成的酶降解的杂化水凝胶在开发用于组织工程的可注射细胞特异性生物活性细胞外基质方面具有巨大的潜力。
