Shi Jiezhong, Wan Yifei, Jia Haoyang, Skeldon Gregor, Jan Cornelissen Dirk, Wesencraft Katrina, Wu Junxi, McConnell Gail, Chen Quan, Liu Dongsheng, Shu Wenmiao
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry Tsinghua University, Beijing, 100084, China.
Department of Biomedical Engineering, University of Strathclyde, Glasgow, G4 0NW, United Kingdom.
Angew Chem Int Ed Engl. 2025 Mar 17;64(12):e202417510. doi: 10.1002/anie.202417510. Epub 2024 Nov 27.
Microvasculature is essential for the continued function of cells in tissue and is fundamental in the fields of tissue engineering, organ repair and drug screening. However, the fabrication of microvasculature is still challenging using existing strategies. Here, we developed a general PRINting Cell Embedded Sacrificial Strategy (PRINCESS) and successfully fabricated microvasculatures using degradable DNA biolubricant. This is the first demonstration of direct cell printing to fabricate microvasculature, which eliminates the need for a subsequent cell seeding process and the associated deficiencies. Utilizing the shear-thinning property of DNA hydrogels as a novel sacrificial, cell-laden biolubricant, we can print a 70 μm endothelialized microvasculature, breaking the limit of 100 μm. To our best knowledge, this is the smallest endothelialized microvasculature that has ever been bioprinted so far. In addition, the self-healing property of DNA hydrogels allows the creation of continuous branched structures. This strategy provides a new platform for constructing complex hierarchical vascular networks and offers new opportunity towards engineering thick tissues. The extremely low volume of sacrificial biolubricant paves the way for DNA hydrogels to be used in practical tissue engineering applications. The high-resolution bioprinting technique also exhibits great potential for printing lymphatics, retinas and neural networks in the future.
微脉管系统对于组织中细胞的持续功能至关重要，并且在组织工程、器官修复和药物筛选领域具有基础性作用。然而，使用现有策略制造微脉管系统仍然具有挑战性。在此，我们开发了一种通用的“打印细胞包埋牺牲策略”（PRINCESS），并使用可降解的DNA生物润滑剂成功制造了微脉管系统。这是首次通过直接细胞打印制造微脉管系统的演示，消除了后续细胞接种过程及相关缺陷。利用DNA水凝胶的剪切变稀特性作为一种新型的牺牲性、负载细胞的生物润滑剂，我们能够打印出70μm的内皮化微脉管系统，突破了100μm的限制。据我们所知，这是迄今为止通过生物打印得到的最小的内皮化微脉管系统。此外，DNA水凝胶的自愈特性使得能够创建连续的分支结构。该策略为构建复杂的分层血管网络提供了一个新平台，并为工程化厚组织提供了新机遇。牺牲性生物润滑剂的极低体积为DNA水凝胶在实际组织工程应用中的使用铺平了道路。这种高分辨率生物打印技术在未来打印淋巴管、视网膜和神经网络方面也显示出巨大潜力。
