摘要
关节软骨损伤、缺损是一种常见且严峻的临床挑战,没有有效的治疗方法,基于胶原蛋白的水凝胶是软骨组织工程的研究热点之一,但在开发具有良好生物相容性且可安全交联的胶原蛋白产品,并提高软骨修复有效性方面仍然存在巨大挑战。将重组Ⅰ型胶原蛋白和重组Ⅲ型胶原蛋白通过EDC/NHS交联,制备了2种水凝胶,均表现出良好的三维孔隙结构以及优异的力学性能和可降解性。研究发现,重组Ⅰ型胶原蛋白水凝胶(Gel-Ⅰ)和重组Ⅲ型胶原蛋白水凝胶(Gel-Ⅲ)能促进人骨髓间充质干细胞(human bone-marrow mesenchymal stem cells,HBMSCs)糖胺聚糖的分泌,Gel-Ⅰ可以显著上调HBMSCs表达COLⅡ基因和SOX9基因,Gel-Ⅲ可以显著上调SOX9基因表达。在兔子膝关节软骨修复模型中,与对照组和Gel-Ⅲ组相比,Gel-Ⅰ组在骨体积大小方面表现出明显优势,软骨下骨已形成并有效恢复,小梁的数量和厚度最高,小梁分布更均匀,并且缺损处新软骨厚度与相邻软骨厚度相同。因此,Gel-Ⅰ在软骨修复有效性以及安全性方面具有极大的临床应用潜力。
Articular cartilage injuries and defects are a common and severe clinical challenge without effective treatment,and collagen-based hydrogels is a hotspot for cartilage tissue engineering,but there are still great challenges in developing collagen products with good biocompatibility and safe cross-linking,and the effectiveness of cartilage repair needs improving.In this study,recombinant type I collagen and recombinant type III collagen were cross-linked by EDC/NHS to prepare injectable hydrogels.The two hydrogels exhibited good three-dimensional pore structures,and excellent mechanical properties as well as degradability.It was found that recombinant type I collagen hydrogel(Gel-Ⅰ) and recombinant type III collagen hydrogel(Gel-Ⅲ) could promote the glycosaminoglycans secretion of HBMSCs.The effects of the hydrogels on the chondrogenic differentiation of HBMSCs were analyzed by RF-qPCR,and it was found that Gel-Ⅰ significantly up-regulated COLII gene and SOX9 gene,and Gel-Ⅲ significantly up-regulated SOX9 gene.In the rabbit knee articular cartilage repair model,compared with the blank and Gel-Ⅲ groups,Gel-Ⅰ group showed the significant advantage in bone volume size,subchondral bone had been formed and effectively restored,the number and thickness of trabeculae were the highest,the trabeculaes were more uniformly distributed,and the thickness of the new cartilage at the defect was the same as that of the neighbouring cartilage.In conclusion,Gel-Ⅰ has great potential for clinical application in terms of the effectiveness and safety of cartilage repair.
作者
黄长瑾
雷桓
唐晓军
HUANG Changjin;LEI Huan;TANG Xiaojun(Hospital of Plastic and Reconstructive Surgery,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100144,China;College of Chemical Engineering,Northwestern University,Xi'an 710069,China;Institute of Biomedical Research,Northwestern University,Xi'an 710069,China)
出处
《中国材料进展》
CAS
CSCD
北大核心
2024年第4期344-354,共11页
Materials China
基金
陕西省可降解生物医学材料重点实验室项目(11JS104,12JS101)。
