Ji Xiongfa, Lei Zehua, Yuan Meng, Zhu Hao, Yuan Xi, Liu Wenbin, Pu Hongxu, Jiang Jiawei, Zhang Yu, Jiang Xulin, Xiao Jun
Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Orthopedics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, PR China.
Theranostics. 2020 Feb 3;10(6):2872-2887. doi: 10.7150/thno.41622. eCollection 2020.
Repairing cartilage defects using thermosensitive hydrogels is an attractive treatment strategy, but the poor mechanical properties and limited understanding of the interactions between hydrogels and cells limit their application. : In this study, a thermosensitive hydroxypropyl chitin hydrogel (HPCH) was functionalized with methacrylate groups to synthesize photocrosslinkable glycidyl methacrylate-modified HPCH (GM-HPCH). GM-HPCH could form a gel through a thermosensitive sol-gel transition and its mechanical properties can be improved by UV irradiation. Cell viability, cell adhesion and anti-apoptosis activity of GM-HPCH were evaluated. Transforming growth factor-β1 (TGFβ1) was introduced into the GM-HPCH hydrogel to fabricate the composite hydrogel. The macrophage immunomodulation, MSC recruitment and chondrogenesis of the composite hydrogel were evaluated. : With high biocompatibility, GM-HPCH could protect chondrocytes from apoptosis. Both the and experiments showed that GM-HPCH + TGFβ1 shifted the recruited macrophages from M1 to M2 and promoted chondrogenic gene expression. Additionally, the composite hydrogel could promote the migration of marrow stromal cells (MSCs) in the Transwell test and increase migrated gene expression. The fluorescent tracking of MSCs confirmed MSC homing in the rat chondral defect with the help of GM-HPCH. The macroscopic evaluation and histological results at 6 weeks and 12 weeks postsurgery showed that GM-HPCH + TGFβ1 can achieve superior cartilage healing. : The GM-HPCH + TGFβ1 hydrogel effectively promoted cartilage repair via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis; thus it is a promising injectable hydrogel for cartilage regeneration.
使用热敏水凝胶修复软骨缺损是一种有吸引力的治疗策略,但水凝胶较差的机械性能以及对其与细胞间相互作用的了解有限,限制了它们的应用。在本研究中,用甲基丙烯酸酯基团对热敏性羟丙基甲壳素水凝胶(HPCH)进行功能化,以合成可光交联的甲基丙烯酸缩水甘油酯改性HPCH(GM-HPCH)。GM-HPCH可通过热敏性溶胶-凝胶转变形成凝胶,并且其机械性能可通过紫外线照射得到改善。评估了GM-HPCH的细胞活力、细胞黏附及抗凋亡活性。将转化生长因子-β1(TGFβ1)引入GM-HPCH水凝胶中以制备复合水凝胶。评估了复合水凝胶的巨噬细胞免疫调节、间充质干细胞募集及软骨形成情况。GM-HPCH具有高生物相容性,可保护软骨细胞免于凋亡。体内和体外实验均表明,GM-HPCH + TGFβ1使募集的巨噬细胞从M1型转变为M2型,并促进软骨生成基因表达。此外,在Transwell实验中,复合水凝胶可促进骨髓基质细胞(MSCs)的迁移并增加迁移基因的表达。MSCs的荧光追踪证实,在GM-HPCH的帮助下,MSCs可归巢至大鼠软骨缺损处。术后6周和12周的宏观评估和组织学结果表明,GM-HPCH + TGFβ1可实现更好的软骨愈合。GM-HPCH + TGFβ1水凝胶通过免疫调节巨噬细胞、募集MSCs和促进软骨形成,有效促进了软骨修复;因此,它是一种有前景的用于软骨再生的可注射水凝胶。