Chen Xiaofang, Aledia Anna S, Ghajar Cyrus M, Griffith Craig K, Putnam Andrew J, Hughes Christopher C W, George Steven C
Department of Biomedical Engineering, University of California Irvine, Irvine, California 92697-2715, USA.
Tissue Eng Part A. 2009 Jun;15(6):1363-71. doi: 10.1089/ten.tea.2008.0314.
One critical obstacle facing tissue engineering is the formation of functional vascular networks that can support tissue survival in vivo. We hypothesized that prevascularizing a tissue construct with networks of well-formed capillaries would accelerate functional anastomosis with the host upon implantation. Fibrin-based tissues were prevascularized with capillary networks by coculturing human umbilical vein endothelial cells (HUVECs) and fibroblasts in fibrin gels for 1 week. The prevascularized tissue and nonprevascularized controls were implanted subcutaneously onto the dorsal surface of immune-deficient mice and retrieved at days 3, 5, 7 and 14. HUVEC-lined vessels containing red blood cells were evident in the prevascularized tissue by day 5, significantly earlier than nonprevascularized tissues (14 days). Analysis of the HUVEC-lined vessels demonstrated that the number and area of perfused lumens in the prevascularized tissue were significantly larger compared to controls. In addition, collagen deposition and a larger number of proliferating cells were evident in the prevascularized tissue at day 14. Our results demonstrate that prevascularizing a fibrin-based tissue with well-formed capillaries accelerates anastomosis with the host vasculature, and promotes cellular activity consistent with tissue remodeling. Our prevascularization strategy may be useful to design large three-dimensional engineered tissues.
组织工程面临的一个关键障碍是形成能够支持体内组织存活的功能性血管网络。我们假设用形态良好的毛细血管网络对组织构建体进行预血管化将在植入时加速与宿主的功能性吻合。通过在纤维蛋白凝胶中将人脐静脉内皮细胞（HUVECs）和成纤维细胞共培养1周，用毛细血管网络对基于纤维蛋白的组织进行预血管化。将预血管化组织和未预血管化的对照皮下植入免疫缺陷小鼠的背部表面，并在第3、5、7和14天取出。到第5天，预血管化组织中含有红细胞的HUVEC内衬血管明显可见，明显早于未预血管化组织（14天）。对HUVEC内衬血管的分析表明，与对照相比，预血管化组织中灌注管腔的数量和面积明显更大。此外，在第14天，预血管化组织中明显可见胶原蛋白沉积和大量增殖细胞。我们的结果表明，用形态良好的毛细血管对基于纤维蛋白的组织进行预血管化可加速与宿主血管系统的吻合，并促进与组织重塑一致的细胞活性。我们的预血管化策略可能有助于设计大型三维工程组织。
