School of Mechanical Engineering and Automation, Harbin Institute of Technology, Shenzhen 518055, China.
Biomanufacturing Engineering Laboratory, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, China.
ACS Appl Mater Interfaces. 2023 Oct 18;15(41):47989-48000. doi: 10.1021/acsami.3c10697. Epub 2023 Oct 5.
Current tissue-engineered tendons are mostly limited to the replication of fibrous organizations of native tendons, which lack the biomimicry of a densely packed cell arrangement. In this study, composite tendon constructs (CTCs) with fibrous arrangement, high cell density, and enhanced cell alignment were developed by integrating the electrohydrodynamic jet 3D printing (e-jetting) technique and the fabrication of tissue strands (TSs). A tubular polycaprolactone (PCL) scaffold was created using e-jetting, followed by coating a thin layer of alginate. Human mesenchymal stem cells were then microinjected into the PCL scaffolds, aggregated into TSs, and formed CTCs with a core-shell structure. Owing to the presence of TSs, CTCs demonstrated the anatomically relevant cell density and morphology, and cells migrated from the TSs onto e-jetted scaffolds. Also, the mechanical strength of CTCs approached that of native tendons due to the existence of e-jetted scaffolds (Young's modulus: ∼21 MPa, ultimate strength: ∼5 MPa). During the entire culture period, CTCs maintained high survival rates and good structural integrity without the observation of necrotic cores and disintegration of two portions. In addition, CTCs that were cultured with uniaxial cyclic stretching revealed not only the increased expression of tendon-related proteins but also the enhanced cellular orientation. The promising results demonstrated the potential of this novel biofabrication strategy for building tissue-engineered tendon constructs with the proper biological, mechanical, and histological relevance..
目前的组织工程肌腱大多局限于复制天然肌腱的纤维组织，缺乏密集排列的细胞结构仿生。在这项研究中，通过整合静电纺丝 3D 打印（e-jetting）技术和组织束（TSs）的制造，开发了具有纤维排列、高细胞密度和增强细胞排列的复合肌腱构建体（CTCs）。使用 e-jetting 制造管状聚己内酯（PCL）支架，然后涂覆一层薄薄的藻酸盐。然后将人骨髓间充质干细胞微注射到 PCL 支架中，聚集形成 TSs，并形成具有核壳结构的 CTCs。由于存在 TSs，CTCs 表现出解剖学上相关的细胞密度和形态，并且细胞从 TSs 迁移到 e-喷射支架上。此外，由于存在 e-喷射支架，CTCs 的机械强度接近天然肌腱（杨氏模量：21 MPa，极限强度：5 MPa）。在整个培养期间，CTCs 保持高存活率和良好的结构完整性，没有观察到坏死核心和两部分的解体。此外，在单向循环拉伸下培养的 CTCs 不仅表现出肌腱相关蛋白表达的增加，而且表现出细胞取向的增强。有前途的结果表明，这种新型生物制造策略具有构建具有适当生物学、机械学和组织学相关性的组织工程肌腱构建体的潜力。
