Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA , Institute of Orthopedics , No. 28 Fuxing Road, Haidian District , Beijing 100853 , People's Republic of China.
Department of Orthopedic Surgery, Beijing Jishuitan Hospital , Peking University Fourth School of Clinical Medicine , No. 31 Xinjiekou East Street, Xicheng District , Beijing 100035 , People's Republic of China.
ACS Appl Mater Interfaces. 2019 Nov 6;11(44):41626-41639. doi: 10.1021/acsami.9b13611. Epub 2019 Oct 22.
Regeneration of an injured meniscus continues to be a scientific challenge due to its poor self-healing potential. Tissue engineering provides an avenue for regenerating a severely damaged meniscus. In this study, we first investigated the superiority of five concentrations (0%, 0.5%, 1%, 2%, and 4%) of meniscus extracellular matrix (MECM)-based hydrogel in promoting cell proliferation and the matrix-forming phenotype of meniscal fibrochondrocytes (MFCs). We found that the 2% group strongly enhanced chondrogenic marker mRNA expression and cell proliferation compared to the other groups. Moreover, the 2% group showed the highest glycosaminoglycan (GAG) and collagen production by day 14. We then constructed a hybrid scaffold by 3D printing a wedge-shaped poly(ε-caprolactone) (PCL) scaffold as a backbone, followed by injection with the optimized MECM-based hydrogel (2%), which served as a cell delivery system. The hybrid scaffold (PCL-hydrogel) clearly yielded favorable biomechanical properties close to those of the native meniscus. Finally, PCL scaffold, PCL-hydrogel, and MFCs-loaded hybrid scaffold (PCL-hydrogel-MFCs) were implanted into the knee joints of New Zealand rabbits that underwent total medial meniscectomy. Six months postimplantation we found that the PCL-hydrogel-MFCs group exhibited markedly better gross appearance and cartilage protection than the PCL scaffold and PCL-hydrogel groups. Moreover, the regenerated menisci in the PCL-hydrogel-MFCs group had similar histological structures, biochemical contents, and biomechanical properties as the native menisci in the sham operation group. In conclusion, PCL-MECM-based hydrogel hybrid scaffold seeded with MFCs can successfully promote whole meniscus regeneration, and cell-loaded PCL-MECM-based hydrogel hybrid scaffold may be a promising strategy for meniscus regeneration in the future.
由于半月板自我修复能力差，半月板损伤的修复仍然是一个科学挑战。组织工程为半月板的再生提供了一种途径。在这项研究中，我们首先研究了 5 种浓度（0%、0.5%、1%、2%和 4%）的半月板细胞外基质（MECM）水凝胶在促进半月板纤维软骨细胞（MFC）增殖和基质形成表型方面的优越性。我们发现，与其他组相比，2%组强烈增强了软骨标志物 mRNA 表达和细胞增殖。此外，2%组在第 14 天表现出最高的糖胺聚糖（GAG）和胶原产生。然后，我们通过 3D 打印楔形聚己内酯（PCL）支架作为支架，然后注射优化的基于 MECM 的水凝胶（2%）构建了混合支架，作为细胞输送系统。混合支架（PCL-水凝胶）明显具有接近天然半月板的有利生物力学性能。最后，将 PCL 支架、PCL-水凝胶和负载 MFC 的混合支架（PCL-水凝胶-MFC）植入接受全内侧半月板切除术的新西兰兔膝关节。植入后 6 个月，我们发现 PCL-水凝胶-MFC 组的大体外观和软骨保护明显优于 PCL 支架和 PCL-水凝胶组。此外，PCL-水凝胶-MFC 组再生的半月板在组织学结构、生化含量和生物力学性能方面与假手术组的天然半月板相似。总之，负载 MFC 的 PCL-MECM 水凝胶混合支架可以成功促进整个半月板再生，负载细胞的 PCL-MECM 水凝胶混合支架可能是未来半月板再生的一种有前途的策略。
