Chitosan-based hydrogels have been extensively used for tissue regeneration due to the excellent biocompatibility and biodegradability. For lack of endogenous extracellular biomacromolecules, its application is obviously limited. Because of robust biological activity, porcine small intestinal submucosa (SIS) has been considered as promising candidates to increase the bioactivity of hydrogels. Herein, a facile method for the fabrication of SIS powders (SISP)/chitosan chloride (CSCl)-β-glycerol phosphate (GP)-hydroxyethyl cellulose (HEC) hydrogel was developed. FTIR imaging results demonstrated that SISP and CSCl could be well mixed to form porous three-dimensional SISP/CSCl composite, which underwent sol-gel phage transition from solution to non-flowing hydrogel at 37 °C. Interestingly, the sustained release of VEGF and b-FGF within the composite hydrogel was determined and no initial burst release was observed. SISP/CSCl composite supported the survival and proliferation of NIH 3T3 cells in vitro and good biocompatibility in the SD rats subcutis up to 8 weeks. Furthermore, incorporated with SISP into CSCl delayed the degradation of SISP in vivo, as characterized by histological and High-Frequency Ultrasound (HFUS) measurement. Thus, all the findings suggested that the newlydeveloped injectable and thermosensitive SISP/CSCl composite was a promising and attractive candidate for soft tissue regeneration in the minimally-invasive way.

中文翻译：

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用于组织工程应用的含细胞外基质颗粒的复合壳聚糖水凝胶的生产与表征。

基于壳聚糖的水凝胶由于其优异的生物相容性和生物降解性而被广泛用于组织再生。由于缺乏内源性细胞外生物大分子，其应用显然受到限制。由于强大的生物活性，猪小肠粘膜下层（SIS）被认为是增加水凝胶生物活性的有前途的候选者。本文中，一种用于制造SIS粉（SISP）/壳聚糖氯化物（CSCl）-β的简便方法开发了磷酸甘油甘油（GP）-羟乙基纤维素（HEC）水凝胶。FTIR成像结果表明，SISP和CSCl可以很好地混合以形成多孔的三维SISP / CSCl复合材料，该复合材料在37°C下经历了溶胶-凝胶噬菌体从溶液到非流动水凝胶的转变。有趣的是，确定了复合水凝胶中VEGF和b-FGF的持续释放，没有观察到初始的突释。SISP / CSCl复合材料可支持NIH 3T3细胞在体外存活和增殖，并支持皮下SD大鼠长达8周的良好生物相容性。此外，将SISP掺入CSCl可以延缓SISP在体内的降解，以组织学和高频超声（HFUS）测量为特征。因此，所有发现均表明，新开发的可注射和热敏SISP / CSCl复合材料是一种以微创方式进行软组织再生的有前途且有吸引力的候选药物。