Pan Xinyao, Liu Sitian, Long Meng, Peng Ruijun, Hu Lanlan, Yu Liu, Huang Wenhua
Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, Department of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, P.R. China.
Biomater Sci. 2025 Aug 19;13(17):4803-4815. doi: 10.1039/d5bm00734h.
Cardiac tissue engineering (CTE) shows great potential for repairing chronic myocardial damage. However, inadequate vascularization in engineered myocardial constructs thicker than 200 μm limits nutrient perfusion and leads to core necrosis, restricting its clinical application. Here, we combine 3D printing with phase separation to fabricate biomimetic vascular scaffolds, polycaprolactone (PCL) tubes, exhibiting enhanced mechanical resilience and biocompatibility. The PCL-tube facilitates the self-assembly of human umbilical vein endothelial cells (HUVECs) into microvascular networks that recapitulate the barrier functions of native vasculature, enabling selective molecular transport while preserving structural integrity. The endothelialized PCL-tube (ECs-PCL-tube) is integrated with cardiomyocyte (CM)-loaded fibrinogen-GelMA (FG) hydrogel through modular assembly to form a multi-scale, vascularized engineered cardiac tissue. The results show that the ECs-PCL-tubes significantly improve cell viability and enhance nutrient perfusion efficiency. Furthermore, the vascularized engineered cardiac tissue exhibited superior CM sarcomere formation, gap junction expression, and contractility, promoting enhanced cell-cell communication. In summary, our study addresses the limitations of lumen collapse and nutrient diffusion in conventional hydrogel systems, offering a scalable and cost-effective solution for constructing functional, vascularized cardiac tissues. This approach holds significant potential for applications in regenerative medicine and drug screening.
心脏组织工程（CTE）在修复慢性心肌损伤方面显示出巨大潜力。然而，厚度超过200μm的工程化心肌构建体中血管化不足限制了营养物质灌注并导致核心坏死，从而限制了其临床应用。在此，我们将3D打印与相分离相结合，制造出具有仿生血管支架的聚己内酯（PCL）管，其具有增强的机械弹性和生物相容性。PCL管促进人脐静脉内皮细胞（HUVECs）自组装成微血管网络，该网络重现了天然脉管系统的屏障功能，在保持结构完整性的同时实现选择性分子运输。内皮化的PCL管（ECs-PCL管）通过模块化组装与负载心肌细胞（CM）的纤维蛋白原-GelMA（FG）水凝胶整合，形成多尺度、血管化的工程化心脏组织。结果表明，ECs-PCL管显著提高细胞活力并增强营养物质灌注效率。此外，血管化的工程化心脏组织表现出优异的CM肌节形成、间隙连接表达和收缩性，促进了增强的细胞间通讯。总之，我们的研究解决了传统水凝胶系统中管腔塌陷和营养物质扩散的局限性，为构建功能性、血管化心脏组织提供了一种可扩展且具有成本效益的解决方案。这种方法在再生医学和药物筛选应用中具有巨大潜力。
