ECM based injectable thermo-sensitive hydrogel on the recovery of injured cartilage induced by osteoarthritis
ECM based injectable thermo-sensitive hydrogel on the recovery of injured cartilage induced by osteoarthritis
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基于 ECM 的可注射热敏水凝胶对骨关节炎引起的损伤软骨的恢复
DOI：
10.1080/21691401.2018.1452752
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发表时间：
2018-01-01
影响因子：
5.8
通讯作者：
Sun, Yong
中科院分区：
文献类型：
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作者：
Li, Yitong;Cao, Jie;Sun, Yong
摘要关节腔内注射抗炎药物是一种很有前途的治疗关节软骨损伤的方法。以Pluronic F127、糖胺聚糖（glycosaminoglycan，GAG）和骨形态发生蛋白（bone morphogenetic protein，BMP-2）为主要成分，制备了一系列可注射温敏复合水凝胶，用于模拟细胞外基质（extracellular matrix，ECM）。研究了含硫酸软骨素和不同相对分子质量（10 k、90 k、800 k）透明质酸的复合水凝胶的流变性能和溶出速率。同时，以牛血清白蛋白（BSA）和FITC-BSA为模型药物，研究了PF/GAG水凝胶的体外缓释行为。结果表明，由于BSA与GAG之间的亲和性，PF/GAG复合凝胶中BSA的释放速率远低于PF 127凝胶。此外，增加透明质酸的分子量相应地增加水凝胶的溶解速率和BSA在水凝胶中的释放。随后，进行MTT实验以研究水凝胶对小鼠前成骨细胞MC 3 T3-E1的毒性。体内抗炎实验结果表明，与对照组（PF127@BMP-2或BMP-2生理盐水溶液）相比，PF/GAG@BMP-2复合水凝胶对骨关节炎引起的软骨损伤具有最有效的修复效果。
Abstract Intra-articular injection of anti-inflammatory drugs can be a promising strategy for recovery of injured articular cartilage. We prepared a series of injectable thermo-sensitive composite hydrogels, composed of Pluronic F127, glycosaminoglycan (GAG) and bone morphogenetic protein (BMP-2), which was designed to mimic extracellular matrix (ECM). The rheological properties and dissolution rate of composite hydrogels containing chondroitin sulfate or with different hyaluronic acid molecular mass (10k, 90k, 800k) were investigated. Meanwhile, bovine serum albumin (BSA) or FITC-BSA was chosen as model drug loaded into PF/GAG hydrogels to study their sustained release behavior in vitro. The results showed that hydrogels could maintain shapes for more than 16 days and the release rate of BSA in PF/GAG composite gels was much slower than in PF127 gels, due to the affinity between BSA and GAG. Furthermore, increasing the molecular weight of hyaluronic acid correspondingly increased hydrogel dissolution rate and BSA release in the hydrogels. Subsequently, MTT experiments were performed to investigate the toxicity of the hydrogels on mouse pre-osteoblast cell MC3T3-E1. In vivo anti-inflammation results showed that PF/GAG@BMP-2 composite hydrogels had the most efficient efficacy on recovery of injured cartilage, which is induced by osteoarthritis, compared to the control groups (PF127@BMP-2 or BMP-2 saline solution).