Department of Bioengineering, University of Washington, USA; Center for Cardiovascular Biology, University of Washington, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, USA.
Department of Bioengineering, University of Washington, USA.
Biomaterials. 2023 Oct;301:122250. doi: 10.1016/j.biomaterials.2023.122250. Epub 2023 Jul 18.
Fabrication of large-scale engineered tissues requires extensive vascularization to support tissue survival and function. Here, we report a modular fabrication approach, by stacking of patterned collagen membranes, to generate thick (2 mm and beyond), large, three-dimensional, perfusable networks of endothelialized vasculature. In vitro, these perfusable vascular networks exhibit remodeling and evenly distributed perfusion among layers, while maintaining their patterned, open-lumen architecture. Compared to non-perfusable, self-assembled vasculature, constructs with perfusable vasculature demonstrated increased gene expression indicative of vascular development and angiogenesis. Upon implantation onto infarcted rat hearts, perfusable vascular networks attain greater host vascular integration than self-assembled controls, indicated by 2.5-fold greater perfused vascular density measured by histological analysis and 5-fold greater perfusion rate measured by optical microangiography. Together, the success of fabricating thick, perfusable tissues with dense vascularity and rapid anastomoses represents an important step forward for vascular bioengineering, and paves the way towards more complex, large scale, highly metabolic engineered tissues.
制造大规模工程组织需要广泛的血管化来支持组织的存活和功能。在这里，我们报告了一种模块化的制造方法，通过堆叠图案化的胶原蛋白膜，来生成厚（2 毫米及以上）、大、三维、可灌注的内皮化脉管网络。在体外，这些可灌注的血管网络表现出重塑和在各层之间均匀分布的灌注，同时保持其图案化的、开放腔的结构。与不可灌注的自组装脉管系统相比，具有可灌注脉管系统的构建体表现出更高的基因表达水平，表明血管发育和血管生成。在植入梗死大鼠心脏后，可灌注的血管网络与自组装对照相比获得了更大的宿主血管整合，这通过组织学分析测量的灌注血管密度增加了 2.5 倍和光学微血管造影测量的灌注率增加了 5 倍来证明。总之，成功地制造出具有密集血管和快速吻合的厚、可灌注组织是血管生物工程的重要一步，为更复杂、大规模、高代谢的工程组织铺平了道路。
