Sarveswaran K, Kurz V, Dong Z, Tanaka T, Penny S, Timp G
Depts. Biological Science and Electrical Engineering, 316 Stinson-Remick Hall, University of Notre Dame, Notre Dame, IN 46556.
Sci Rep. 2016 Feb 24;6:21885. doi: 10.1038/srep21885.
Capillaries pervade human physiology. The mean intercapillary distance is only about 100 μm in human tissue, which indicates the extent of nutrient diffusion. In engineered tissue the lack of capillaries, along with the associated perfusion, is problematic because it leads to hypoxic stress and necrosis. However, a capillary is not easy to engineer due to its complex cytoarchitecture. Here, it is shown that it is possible to create in vitro, in about 30 min, a tubular microenvironment with an elastic modulus and porosity consistent with human tissue that functionally mimicks a bona fide capillary using "live cell lithography"(LCL) to control the type and position of cells on a composite hydrogel scaffold. Furthermore, it is established that these constructs support the forces associated with blood flow, and produce nutrient gradients similar to those measured in vivo. With LCL, capillaries can be constructed with single cell precision-no other method for tissue engineering offers such precision. Since the time required for assembly scales with the number of cells, this method is likely to be adapted first to create minimal functional units of human tissue that constitute organs, consisting of a heterogeneous population of 100-1000 cells, organized hierarchically to express a predictable function.
毛细血管遍布人体生理系统。人体组织中毛细血管的平均间距仅约100微米，这表明了营养物质扩散的程度。在工程组织中，缺乏毛细血管以及相关的灌注是个问题，因为这会导致缺氧应激和坏死。然而，由于毛细血管复杂的细胞结构，很难对其进行工程构建。在此，研究表明，使用“活细胞光刻”（LCL）来控制复合水凝胶支架上细胞的类型和位置，能够在大约30分钟内在体外创建一个具有与人体组织一致的弹性模量和孔隙率的管状微环境，该微环境在功能上模拟真正的毛细血管。此外，已证实这些构建体能够承受与血流相关的力，并产生与体内测量结果相似的营养物质梯度。通过LCL，可以以单细胞精度构建毛细血管——没有其他组织工程方法能提供如此高的精度。由于组装所需时间与细胞数量成正比，这种方法可能首先适用于创建构成器官的人体组织最小功能单元，这些单元由100 - 1000个异质细胞群体组成，按层次组织以表达可预测的功能。
