Sang Shengbo, Mao Xingjia, Cao Yanyan, Liu Zixian, Shen Zhizhong, Li Meng, Jia Wendan, Guo Zijian, Wang Zehua, Xiang Chuan, Sun Lei
Shanxi Key Laboratory of Micro Nano Sensors & Artificial Intelligence Perception, College of Information and Computer, Taiyuan University of Technology, Taiyuan 030024, China.
Key Lab of Advanced Transducers and Intelligent Control System of the Ministry of Education, Taiyuan University of Technology, Taiyuan 030024, China.
ACS Appl Mater Interfaces. 2023 Feb 13. doi: 10.1021/acsami.2c19058.
In this study, inspired by the components of cartilage matrix, a photo-cross-linked extracellular matrix (ECM) bioink composed of modified proteins and polysaccharides was presented, including gelatin methacrylate, hyaluronic acid methacrylate, and chondroitin sulfate methacrylate. The systematic experiments were performed, including morphology, swelling, degradation, mechanical and rheological tests, printability analysis, biocompatibility and chondrogenic differentiation characterization, and RNA sequencing (RNA-seq). The results indicated that the photo-cross-linked ECM hydrogels possessed suitable degradation rate and excellent mechanical properties, and the three-dimensional (3D) bioprinted ECM scaffolds obtained favorable shape fidelity and improved the basic properties, biological properties, and chondrogenesis of synovium-derived MSCs (SMSCs). The strong stimulation of transforming growth factor-beta 1 (TGF-β1) enhanced the aggregation, proliferation, and differentiation of SMSCs, thereby enhancing chondrogenic ECM deposition. animal experiments and gait analysis further confirmed that the ECM scaffold combined with TGF-β1 could effectively promote cartilage regeneration and functional recovery of injured joints. To sum up, the photo-cross-linked ECM bioink for 3D printing of functional cartilage tissue may become an attractive strategy for cartilage regeneration.
在本研究中，受软骨基质成分的启发，提出了一种由改性蛋白质和多糖组成的光交联细胞外基质（ECM）生物墨水，包括甲基丙烯酸明胶、甲基丙烯酸透明质酸和甲基丙烯酸硫酸软骨素。进行了系统实验，包括形态学、肿胀、降解、力学和流变学测试、可打印性分析、生物相容性和软骨生成分化表征以及RNA测序（RNA-seq）。结果表明，光交联的ECM水凝胶具有合适的降解速率和优异的力学性能，三维（3D）生物打印的ECM支架具有良好的形状保真度，并改善了滑膜来源的间充质干细胞（SMSCs）的基本性能、生物学性能和软骨生成能力。转化生长因子-β1（TGF-β1）的强烈刺激增强了SMSCs的聚集、增殖和分化，从而增强了软骨生成性ECM的沉积。动物实验和步态分析进一步证实，ECM支架与TGF-β1联合应用可有效促进损伤关节的软骨再生和功能恢复。综上所述，用于3D打印功能性软骨组织的光交联ECM生物墨水可能成为一种有吸引力的软骨再生策略。
