Wei Qiang, Liu Dachuan, Chu Genglei, Yu Qifan, Liu Zhao, Li Jiaying, Meng Qingchen, Wang Weishan, Han Fengxuan, Li Bin
Department of Orthopaedic Surgery, Orthopaedic Institute, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
Department of Orthopaedic Surgery, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Bioact Mater. 2022 May 10;19:581-593. doi: 10.1016/j.bioactmat.2022.04.025. eCollection 2023 Jan.
Annulus fibrosus (AF) repair remains a challenge because of its limited self-healing ability. Endogenous repair strategies combining scaffolds and growth factors show great promise in AF repair. Although the unique and beneficial characteristics of decellularized extracellular matrix (ECM) in tissue repair have been demonstrated, the poor mechanical property of ECM hydrogels largely hinders their applications in tissue regeneration. In the present study, we combined polyethylene glycol diacrylate (PEGDA) and decellularized annulus fibrosus matrix (DAFM) to develop an injectable, photocurable hydrogel for AF repair. We found that the addition of PEGDA markedly improved the mechanical strength of DAFM hydrogels while maintaining their porous structure. Transforming growth factor-β1 (TGF-β1) was further incorporated into PEGDA/DAFM hydrogels, and it could be continuously released from the hydrogel. The experiments showed that TGF-β1 facilitated the migration of AF cells. Furthermore, PEGDA/DAFM/TGF-β1 hydrogels supported the adhesion, proliferation, and increased ECM production of AF cells. repair performance of the hydrogels was assessed using a rat AF defect model. The results showed that the implantation of PEGDA/DAFM/TGF-β1 hydrogels effectively sealed the AF defect, prevented nucleus pulposus atrophy, retained disc height, and partially restored the biomechanical properties of disc. In addition, the implanted hydrogel was infiltrated by cells resembling AF cells and well integrated with adjacent AF tissue. In summary, findings from this study indicate that TGF-β1-supplemented DAFM hydrogels hold promise for AF repair.
由于纤维环(AF)的自我修复能力有限,其修复仍然是一项挑战。结合支架和生长因子的内源性修复策略在AF修复中显示出巨大潜力。尽管已证明脱细胞细胞外基质(ECM)在组织修复中具有独特且有益的特性,但ECM水凝胶较差的机械性能在很大程度上阻碍了它们在组织再生中的应用。在本研究中,我们将聚乙二醇二丙烯酸酯(PEGDA)与脱细胞纤维环基质(DAFM)相结合,开发出一种用于AF修复的可注射、光固化水凝胶。我们发现添加PEGDA可显著提高DAFM水凝胶的机械强度,同时保持其多孔结构。将转化生长因子-β1(TGF-β1)进一步掺入PEGDA/DAFM水凝胶中,它可以从水凝胶中持续释放。实验表明,TGF-β1促进了AF细胞的迁移。此外,PEGDA/DAFM/TGF-β1水凝胶支持AF细胞的黏附、增殖并增加其细胞外基质的产生。使用大鼠AF缺损模型评估了水凝胶的修复性能。结果表明,植入PEGDA/DAFM/TGF-β1水凝胶有效地封闭了AF缺损,防止了髓核萎缩,保持了椎间盘高度,并部分恢复了椎间盘的生物力学性能。此外,植入的水凝胶被类似AF细胞的细胞浸润,并与相邻的AF组织良好整合。总之,本研究结果表明,补充TGF-β1的DAFM水凝胶在AF修复方面具有潜力。