Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China; Department of Prosthodontics, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Clinical and Translational Research Center for 3D Printing Technology, Medical 3D Printing Innovation Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China; Department of Orthopaedic Surgery, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Biomaterials. 2021 Jul;274:120841. doi: 10.1016/j.biomaterials.2021.120841. Epub 2021 Apr 30.
Mesenchymal stem cells (MSCs) secrete paracrine trophic factors that are beneficial for tissue regeneration. In this study, a sponge-like scaffold with hierarchical and interconnected pores was developed using low-temperature deposition modeling (LDM) printing. Its effects on the cellular behavior, especially on the paracrine secretion patterns of MSCs, were comprehensively investigated. We found that compared with the scaffolds printed via the fused deposition modeling (FDM) technique, the LDM-printed sponges enhanced the adhesion, retention, survival, and ingrowth of MSCs and promoted cell-material interactions. Moreover, the paracrine functions of the cultured MSCs on the LDM-printed sponges were improved, with significant secretion of upregulated immunomodulatory, angiogenic, and osteogenic factors. MSCs on the LDM-printed sponges exert beneficial paracrine effects on multiple regenerative processes, including macrophage polarization, tube formation, and osteogenesis, verifying the enhanced immunomodulatory, angiogenic, and osteogenic potential. Further protein function assays indicated that focal adhesion kinase (FAK), downstream AKT, and yes-associated-protein (YAP) signaling might participate in the required mechanotransductive pathways, through which the hierarchical porous structures stimulated the paracrine effects of MSCs. In a rat distal femoral defect model, the MSC-laden LDM-printed sponges significantly promoted vascularized bone regeneration. The results of the present study demonstrate that the hierarchical porous biomimetic sponges prepared via LDM printing have potential applications in tissue engineering based on their cell-material interaction promotion and MSC paracrine function modulation effects. Furthermore, our findings suggest that the optimization of biomaterial properties to direct the paracrine signaling of MSCs would enhance tissue regeneration.
间充质干细胞 (MSCs) 分泌旁分泌营养因子，有利于组织再生。在这项研究中，使用低温沉积建模 (LDM) 打印开发了具有层次化和互连孔的海绵状支架。全面研究了其对细胞行为的影响，特别是对 MSCs 旁分泌分泌模式的影响。我们发现，与通过熔丝制造 (FDM) 技术打印的支架相比，LDM 打印的海绵增强了 MSCs 的粘附、保留、存活和向内生长，并促进了细胞-材料相互作用。此外，培养的 MSCs 在 LDM 打印的海绵上的旁分泌功能得到改善，上调的免疫调节、血管生成和成骨因子显著分泌。LDM 打印的海绵上的 MSCs 对多种再生过程产生有益的旁分泌作用，包括巨噬细胞极化、管形成和成骨作用，验证了增强的免疫调节、血管生成和成骨潜力。进一步的蛋白质功能测定表明，粘着斑激酶 (FAK)、下游 AKT 和 yes 相关蛋白 (YAP) 信号通路可能参与所需的机械转导途径，通过该途径，分层多孔结构刺激 MSCs 的旁分泌作用。在大鼠股骨远端缺损模型中，负载 MSC 的 LDM 打印海绵显著促进了血管化骨再生。本研究结果表明，通过 LDM 打印制备的分层多孔仿生海绵具有促进细胞-材料相互作用和调节 MSC 旁分泌功能的潜力，在组织工程中有应用前景。此外，我们的研究结果表明，优化生物材料特性以指导 MSCs 的旁分泌信号可能会增强组织再生。
