Lammers Alex, Hsu Heng-Hua, Sundaram Subramanian, Gagnon Keith A, Kim Sudong, Lee Joshua H, Tung Yi-Chung, Eyckmans Jeroen, Chen Christopher S
The Biological Design Center and Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Matter. 2024 Jun 5;7(6):2184-2204. doi: 10.1016/j.matt.2024.04.001. Epub 2024 Apr 23.
Tissue engineering has long sought to rapidly generate perfusable vascularized tissues with vessel sizes spanning those seen in humans. Current techniques such as biological 3D printing (top-down) and cellular self-assembly (bottom-up) are resource intensive and have not overcome the inherent tradeoff between vessel resolution and assembly time, limiting their utility and scalability for engineering tissues. We present a flexible and scalable technique termed SPAN - acrificial ercolation of nisotropic etworks, where a network of perfusable channels is created throughout a tissue in minutes, irrespective of its size. Conduits with length scales spanning arterioles to capillaries are generated using pipettable alginate fibers that interconnect above a percolation density threshold and are then degraded within constructs of arbitrary size and shape. SPAN is readily used within common tissue engineering processes, can be used to generate endothelial cell-lined vasculature in a multi-cell type construct, and paves the way for rapid assembly of perfusable tissues.
长期以来，组织工程一直致力于快速生成具有不同血管大小（涵盖人类可见血管大小范围）的可灌注血管化组织。当前的技术，如生物3D打印（自上而下）和细胞自组装（自下而上），资源消耗大，且尚未克服血管分辨率与组装时间之间固有的权衡问题，限制了它们在组织工程中的实用性和可扩展性。我们提出了一种灵活且可扩展的技术，称为SPAN——各向异性网络的牺牲性渗滤，该技术可在数分钟内在整个组织中创建一个可灌注通道网络，而不论组织大小。使用可移液的藻酸盐纤维生成长度尺度从微动脉到毛细血管的导管，这些纤维在高于渗滤密度阈值时相互连接，然后在任意大小和形状的构建体中降解。SPAN可轻松应用于常见的组织工程过程，可用于在多细胞类型构建体中生成内皮细胞衬里的脉管系统，并为快速组装可灌注组织铺平了道路。
