Adv. Funct. Mater. 2022, 32, 2200710

骨软骨组织在细胞、组成、结构和机械性质上表现出从软骨到软骨下骨的多个形态学梯度。这种梯度组织是在发育过程中形成的。由于组织排列差异和各向异性生理特征，骨软骨组织的再生仍然具有挑战性。因此，开发一种兼具生物力学和生化梯度的异质结构，以模拟骨软骨微环境，实现软骨和软骨下骨的同步再生具有重要意义。总体而言，开发用于异质结构的3D生物打印的生物墨水，同时获得满足的生物力学和生化梯度，对于骨软骨再生至关重要。

在本文中，敖英芳教授和蔡晴教授的联合团队开发了一种新型的宿主 – 客体双网络水凝胶生物墨水，由多巴胺修饰的GelMA（GelMA-DA），GelMA和丙烯酸酯β环糊精（Ac-β-CD）组成。Ac-β-CD和多巴胺侧基能够形成宿主 – 客体配合物以作为动态交联键，赋予水凝胶优异的韧性和弹性，而水凝胶的机械强度则通过乙烯基团的聚合得到增强。调节乙烯聚合物的浓度为构建具有机械梯度的骨软骨结构提供了可行性。此外，多余的Ac-β-CD可用于封装生物活性药物，从而实现长期的持续释放。携带的干细胞可以在水凝胶网络中自由扩散和迁移，在局部微环境中MLT/KGN持续释放的引导下分泌不同的胶原蛋白，为完成分层ECM和骨软骨排列的沉积提供了动力，最终实现了全层骨软骨再生。

 Osteochondral tissue exhibits multiple morphological gradients from cartilage to subchondral bone in terms of cell, composition, structure and mechanical properties. This gradient organization is formed during development. Regeneration of osteochondral tissue remains challenging due to differential tissue arrangement and anisotropic physiological features. Therefore, it is of great significance to develop a heterogeneous structure with both biomechanical and biochemical gradients to simulate the osteochondral microenvironment and achieve simultaneous regeneration of cartilage and subchondral bone. Overall, the development of bioinks for 3D bioprinting of heterogeneous structures, while obtaining satisfied biomechanical and biochemical gradients, is essential for osteochondral regeneration.

In this paper, the joint team of Professor Ao Yingfang and Professor CAI Qing developed a novel dual-network host-guest hydrogel bioink composed of dopamine-modified GelMA (GELMA-DA), GelMA and acrylate β-cyclodextrin (AC-β-CD). Ac-β-cd and dopamine side groups can form host-guest complexes to act as dynamic cross-linking bonds, endowing hydrogels with excellent toughness and elasticity, while the mechanical strength of hydrogels is enhanced by the polymerization of ethylene groups. It is feasible to construct osteochondral structures with mechanical gradients by adjusting the concentration of ethylene polymer. In addition, excess AC-β-CD can be used to encapsulate bioactive drugs for sustained long-term release. The carried stem cells can freely diffuse and migrate in the hydrogel network, and secrete different collagens under the guidance of the continuous release of MLT/KGN in the local microenvironment, which provides the power to complete the deposition of layered ECM and osteochondral arrangement, and finally realize the full-thickness osteochondral regeneration.

https://doi.org/10.1002/adfm.202200710

DOI:10.1002/adfm.202200710

郭子渊