Wang Xinhuan, Liu Xin, Li Kai, Liu Wenli, Wang Yifan, Ji Shen, Gao Zili, Ren Jilong, Hai Tang, Hui Lijian, Zheng Xiongfei, Gu Qi
Human Organ Physiopathology Emulation System, State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, P. R. China.
Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, P. R. China.
Adv Mater. 2025 Jul;37(28):e2413940. doi: 10.1002/adma.202413940. Epub 2025 Apr 13.
3D bioprinting of liver tissue with high cell density (HCD) shows great promise for restoring function in cases of acute liver failure, where a substantial number of functional cells are required to perform essential physiological tasks. Direct vascular anastomosis is critical for the successful implantation of these bioprinted vascularized tissues into the host vasculature, allowing for rapid functional compensation and addressing various acute conditions. However, conventional hydrogels used to encapsulate high-density cells often lack the mechanical properties needed to withstand the shear forces of physiological blood flow, often resulting in implantation failure. In this study, a heterogeneous microgel-hydrogel hybrid is developed to carry HCD hepatocytes and support the embedded bioprinting of hierarchical vascular structures. By optimizing the ratio of microgel to biomacromolecule, the covalently crosslinked network offers mechanical integrity and enables direct vascular anastomosis, ensuring efficient nutrient and oxygen exchange. The bioprinted thick, vascularized constructs, containing HCD hepatocytes, are successfully implanted in rats after 85% hepatectomy, leading to swift functional recovery and prolonged survival. This study presents a strategy to enhance regenerative therapy outcomes through advanced bioprinting and vascular integration techniques.
具有高细胞密度（HCD）的肝脏组织的3D生物打印在恢复急性肝衰竭病例的功能方面显示出巨大潜力，在急性肝衰竭病例中，需要大量功能细胞来执行基本生理任务。直接血管吻合对于将这些生物打印的血管化组织成功植入宿主脉管系统至关重要，这有助于快速进行功能补偿并应对各种急性病症。然而，用于封装高密度细胞的传统水凝胶通常缺乏承受生理血流剪切力所需的机械性能，常常导致植入失败。在本研究中，开发了一种异质微凝胶-水凝胶杂化物来承载HCD肝细胞并支持分层血管结构的嵌入式生物打印。通过优化微凝胶与生物大分子的比例，共价交联网络提供了机械完整性，并实现了直接血管吻合，确保了有效的营养和氧气交换。含有HCD肝细胞的生物打印厚壁血管化构建体在大鼠85%肝切除术后成功植入，从而实现了快速的功能恢复和延长生存期。本研究提出了一种通过先进的生物打印和血管整合技术来提高再生治疗效果的策略。
