Chen Mingxue, Li YangYang, Liu Shuyun, Feng Zhaoxuan, Wang Hao, Yang Dejin, Guo Weimin, Yuan Zhiguo, Gao Shuang, Zhang Yu, Zha Kangkang, Huang Bo, Wei Fu, Sang Xinyu, Tian Qinyu, Yang Xuan, Sui Xiang, Zhou Yixin, Zheng Yufeng, Guo Quanyi
Department of Orthopaedic Surgery, Peking University Fourth School of Clinical Medicine, Beijing Jishuitan Hospital, No. 31 Xinjiekou East Street, Xicheng District, Beijing, 100035, People's Republic of China.
Institute of Orthopedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No.28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.
Bioact Mater. 2020 Dec 22;6(7):1932-1944. doi: 10.1016/j.bioactmat.2020.12.009. eCollection 2021 Jul.
Tissue engineering provides a promising avenue for treating cartilage defects. However, great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and regeneration. In this study, decellularized cartilage extracellular matrix (ECM) and waterborne polyurethane (WPU) were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing (LDM) system, which combines rapid deposition manufacturing with phase separation techniques. The scaffolds successfully achieved hierarchical macro-microporous structures. After adding ECM, WPU scaffolds were markedly optimized in terms of porosity, hydrophilia and bioactive components. Moreover, the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution, adhesion, and proliferation than the WPU scaffolds. Most importantly, the WPU-ECM scaffold could facilitate the production of glycosaminoglycan (GAG) and collagen and the upregulation of cartilage-specific genes. These results indicated that the WPU-ECM scaffold with hierarchical macro-microporous structures could recreate a favorable microenvironment for cell adhesion, proliferation, differentiation, and ECM production. studies further revealed that the hierarchical macro-microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit model. Six months after implantation, the repaired cartilage showed a similar histological structure and mechanical performance to that of normal cartilage. In conclusion, the hierarchical macro-microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.
组织工程为治疗软骨缺损提供了一条有前景的途径。然而，在开发用于软骨修复和再生的结构和功能优化支架方面，仍存在巨大挑战。在本研究中，采用脱细胞软骨细胞外基质（ECM）和水性聚氨酯（WPU），通过使用低温沉积制造（LDM）系统的水基3D打印构建WPU和WPU-ECM支架，该系统将快速沉积制造与相分离技术相结合。这些支架成功实现了分级宏观-微观多孔结构。添加ECM后，WPU支架在孔隙率、亲水性和生物活性成分方面得到了显著优化。此外，发现优化后的WPU-ECM支架比WPU支架更适合细胞分布、黏附和增殖。最重要的是，WPU-ECM支架可促进糖胺聚糖（GAG）和胶原蛋白的产生以及软骨特异性基因的上调。这些结果表明，具有分级宏观-微观多孔结构的WPU-ECM支架可为细胞黏附、增殖、分化和ECM产生重新创造一个有利的微环境。 研究进一步表明，分级宏观-微观多孔WPU-ECM支架与微骨折手术相结合，在兔模型中成功再生了透明软骨。植入6个月后，修复的软骨显示出与正常软骨相似的组织学结构和力学性能。总之，分级宏观-微观多孔WPU-ECM支架可能是未来软骨组织工程应用的一个有前景的候选材料。
