College of Mechanical Engineering, Dongguan University of Technology, Dongguan, Guangdong, People's Republic of China. Contributed equally. Authors to whom any correspondence should be addressed.
Biofabrication. 2020 Mar 23;12(2):025030. doi: 10.1088/1758-5090/ab7ab5.
Due to the increasing aging population and the high probability of sport injury among young people nowadays, it is of great demand to repair/regenerate diseased/defected osteochondral tissue. Given that osteochondral tissue mainly consists of a subchondral layer and a cartilage layer which are structurally heterogeneous and mechanically distinct, developing a biomimetic bi-phasic scaffold with excellent bonding strength to regenerate osteochondral tissue is highly desirable. Three-dimensional (3D) printing is advantageous in producing scaffolds with customized shape, designed structure/composition gradients and hence can be used to produce heterogeneous scaffolds for osteochondral tissue regeneration. In this study, bi-layered osteochondral scaffolds were developed through cryogenic 3D printing, in which osteogenic peptide/β-tricalcium phosphate/poly(lactic-co-glycolic acid) water-in-oil composite emulsions were printed into hierarchically porous subchondral layer while poly(D,L-lactic acid-co-trimethylene carbonate) water-in-oil emulsions were printed into thermal-responsive cartilage frame on top of the subchondral layer. The cartilage frame was further filled/dispensed with transforming growth factor-β1 loaded collagen I hydrogel to form the cartilage module. Although the continuously constructed osteochondral scaffolds had distinct microscopic morphologies and varied mechanical properties at the subchondral zone and cartilage zone at 37 °C, respectively, the two layers were closely bonded together, showing excellent shear strength and peeling strength. Rat bone marrow derived mesenchymal stem cells (rBMSCs) exhibited high viability and proliferation at both subchondral- and cartilage layer. Moreover, gradient rBMSC osteogenic/chondrogenic differentiation was obtained in the osteochondral scaffolds. This proof-of-concept study provides a facile way to produce integrated osteochondral scaffolds for concurrently directing rBMSC osteogenic/chondrogenic differentiation at different regions.
由于人口老龄化的增加和当今年轻人运动损伤的高概率，修复/再生患病/有缺陷的骨软骨组织的需求很大。鉴于骨软骨组织主要由软骨下层和软骨层组成，其结构不均匀且力学性质不同，因此，开发具有优异结合强度的仿生双相支架来再生骨软骨组织是非常需要的。三维（3D）打印在生产具有定制形状、设计的结构/组成梯度的支架方面具有优势，因此可用于生产用于骨软骨组织再生的异质支架。在这项研究中，通过低温 3D 打印开发了双层骨软骨支架，其中成骨肽/β-磷酸三钙/聚（乳酸-共-乙醇酸）水包油复合乳液被打印成具有分级多孔的软骨下层，而聚（D，L-乳酸-共-三亚甲基碳酸酯）水包油乳液则打印成软骨框架在软骨下层的顶部。软骨框架进一步填充/分配负载转化生长因子-β1的胶原 I 水凝胶以形成软骨模块。尽管连续构建的骨软骨支架在 37°C 时分别在软骨下区和软骨区具有明显的微观形态和不同的机械性能，但两层紧密结合在一起，表现出优异的剪切强度和剥离强度。大鼠骨髓间充质干细胞（rBMSCs）在软骨下层和软骨层均表现出高活力和增殖。此外，在骨软骨支架中获得了梯度 rBMSC 成骨/软骨分化。这项概念验证研究提供了一种简便的方法来生产集成的骨软骨支架，以在不同区域同时指导 rBMSC 成骨/软骨分化。
