Chondrogenic differentiation of BMSCs encapsulated in chondroinductive polysaccharide/collagen hybrid hydrogels.
Chondrogenic differentiation of BMSCs encapsulated in chondroinductive polysaccharide/collagen hybrid hydrogels.
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DOI：
10.1039/c7tb01020f
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发表时间：
2017-07
期刊：
影响因子：
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通讯作者：
Xiupeng Li;Y. Teng;Jun Liu;Hai Lin;Yujiang Fan;Xing‐dong Zhang
中科院分区：
文献类型：
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作者：
Xiupeng Li;Y. Teng;Jun Liu;Hai Lin;Yujiang Fan;Xing‐dong Zhang
虽然基于BMSC的治疗是软骨修复的最前沿技术之一，但要获得理想的BMSC软骨分化的小生境仍然是一个很大的挑战。在本研究中，我们开发了透明质酸和硫酸软骨素衍生物，以制备共价交联多糖水凝胶。在二元水凝胶的基础上，加入胶原蛋白制备三元杂化水凝胶，研究其对包埋骨髓基质细胞的影响。在不添加生长因子的情况下，以不同细胞密度体外培养3周后，通过激光共聚焦扫描显微镜（CLSM）、力学测试、组织学染色、免疫组化染色和基因表达等方法评价BMSCs的成软骨能力。结果表明，高细胞密度（5000万/mL）的BMSCs比低细胞密度（5000万/mL）的BMSCs具有更明显的成软骨表型。然而，水凝胶的组分对软骨分化有显著影响。体外培养3周后，加入胶原的三元杂化水凝胶中的BMSCs具有更显著的软骨形成能力，具有更多的糖胺聚糖（GAGs）分泌和II型胶原沉积，更高的力学性能和软骨形成基因表达。结论：生物活性胶原蛋白有利于骨髓基质细胞的成软骨作用。该复合水凝胶在组织工程软骨缺损修复中具有广阔的应用前景，值得进一步研究。
Although BMSC-based therapy is one of the most front-line technologies for cartilage repair, it is still a big challenge to attain ideal niches for BMSC chondrogenic differentiation. In this study, we developed hyaluronate and chondroitin sulfate derivatives to prepare covalently crosslinked polysaccharide hydrogels. Based on these binary hydrogels, collagen was added to prepare ternary hybrid hydrogels and its effect on encapsulated BMSCs was studied. After culturing with different cell densities in vitro without the addition of growth factors for 3 weeks, the chondrogenesis of BMSCs was evaluated by CLSM, mechanical testing, histological staining, immunohistochemical staining and gene expression. The results indicated that BMSCs in high cell density (50 million per mL) cell-laden constructs had a more obvious chondrogenic phenotype than those in low cell density ones (5 million per mL). However, the components of hydrogels had a significant influence on chondrogenic differentiation. With the addition of collagen, the BMSCs in ternary hybrid hydrogels showed more significant chondrogenesis, possessing with more amounts of secreted glycosaminoglycans (GAGs) and type II collagen deposition, higher mechanical properties and chondrogenic gene expression over 3 weeks of culture in vitro. It can be concluded that the bioactive collagen is beneficial to the chondrogenesis of BMSCs. This hybrid hydrogels deserve further studies to have a prospective application in tissue engineering for cartilage defect repair.