EDC/NHS交联重组胶原蛋白水凝胶修复关节软骨缺损
Study on the Repair of Articular Cartilage Defects by EDC/NHS Cross-Linked Recombinant Collagen Hydrogel
黄长瑾 1雷桓 2唐晓军1
作者信息
- 1. 中国医学科学院北京协和医学院 整形外科医院, 北京 100144
- 2. 西北大学化工学院, 陕西 西安 710069;西北大学 生物医药研究院, 陕西 西安 710069
- 折叠
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.
Abstract
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 in-jectable 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 COL Ⅱ gene and SOX9 gene,and Gel-Ⅲ signifi-cantly 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 distribu-ted,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.
关键词
EDC/NHS/交联/重组胶原蛋白/可注射水凝胶/关节软骨修复Key words
EDC/NHS/cross-linking/recombinant collagen/injectable hydrogel/articular cartilage repair引用本文复制引用
基金项目
陕西省可降解生物医学材料重点实验室项目(11JS104)
陕西省可降解生物医学材料重点实验室项目(12JS101)
出版年
2024
NETL
NSTL
万方数据