Zhang Yijian, Li Duo, Liu Yang, Peng Liuqi, Lu Dongdong, Wang Pinpin, Ke Dongxu, Yang Huilin, Zhu Xuesong, Ruan Changshun
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China.
Research Center for Human Tissue and Organ Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Innovation (Camb). 2023 Nov 20;5(1):100542. doi: 10.1016/j.xinn.2023.100542. eCollection 2024 Jan 8.
Reconstruction of osteochondral (OC) defects represents an immense challenge due to the need for synchronous regeneration of special stratified tissues. The revolutionary innovation of bioprinting provides a robust method for precise fabrication of tissue-engineered OCs with hierarchical structure; however, their spatial living cues for simultaneous fulfilment of osteogenesis and chondrogenesis to reconstruct the cartilage-bone interface of OC are underappreciated. Here, inspired by natural OC bilayer features, anisotropic bicellular living hydrogels (ABLHs) simultaneously embedding articular cartilage progenitor cells (ACPCs) and bone mesenchymal stem cells (BMSCs) in stratified layers were precisely fabricated via two-channel extrusion bioprinting. The optimum formulation of the 7% GelMA/3% AlgMA hydrogel bioink was demonstrated, with excellent printability at room temperature and maintained high cell viability. Moreover, the chondrogenic ability of ACPCs and the osteogenic ability of BMSCs were demonstrated , confirming the inherent differential spatial regulation of ABLHs. In addition, ABLHs exhibited satisfactory synchronous regeneration of cartilage and subchondral bone . Compared with homogeneous hydrogels, the neo-cartilage and neo-bone in ABLHs were augmented by 23.5% and 20.8%, respectively, and more important, a more harmonious cartilage-bone interface was achieved by ABLHs due to their well-tuned cartilage-bone-vessel crosstalk. We anticipate that such a strategy of tissue-mimetic ABLH by means of bioprinting is capable of spatiotemporal cell-driven regeneration, offering insights into the fabrication of anisotropic living materials for the reconstruction of complex organ defects.
由于需要同步再生特殊的分层组织，骨软骨（OC）缺损的修复是一项巨大的挑战。生物打印的革命性创新为精确制造具有分层结构的组织工程化OC提供了一种强大的方法；然而，它们在同时实现成骨和软骨生成以重建OC的软骨-骨界面方面的空间生存线索却未得到充分重视。在此，受天然OC双层特征的启发，通过双通道挤出生物打印精确制造了同时将关节软骨祖细胞（ACPCs）和骨间充质干细胞（BMSCs）分层嵌入的各向异性双细胞活性水凝胶（ABLHs）。证明了7% GelMA/3% AlgMA水凝胶生物墨水的最佳配方，其在室温下具有优异的可打印性并保持高细胞活力。此外，证明了ACPCs的软骨生成能力和BMSCs的成骨能力，证实了ABLHs固有的差异空间调节作用。此外，ABLHs表现出令人满意的软骨和软骨下骨同步再生。与均匀水凝胶相比，ABLHs中的新软骨和新骨分别增加了23.5%和20.8%，更重要的是，由于其良好调节的软骨-骨-血管串扰，ABLHs实现了更和谐的软骨-骨界面。我们预计，这种通过生物打印模拟组织的ABLH策略能够实现时空细胞驱动的再生，为制造用于修复复杂器官缺损的各向异性活性材料提供见解。
