Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Biomaterials. 2020 Feb;230:119634. doi: 10.1016/j.biomaterials.2019.119634. Epub 2019 Nov 18.
There is a critical need for biomaterials that support robust neovascularization for a wide-range of clinical applications. Here we report how cells alter tissue-level mechanical properties during capillary morphogenesis using a model of endothelial-stromal cell co-culture within poly(ethylene glycol) (PEG) based hydrogels. After a week of culture, we observed substantial stiffening in hydrogels with very soft initial properties. Endothelial cells or stromal cells alone, however, failed to induce hydrogel stiffening. This stiffening tightly correlated with degree of vessel formation but not with hydrogel compaction or cellular proliferation. Despite a lack of fibrillar architecture within the PEG hydrogels, cell-generated contractile forces were essential for hydrogel stiffening. Upregulation of alpha smooth muscle actin and collagen-1 was also correlated with enhanced vessel formation and hydrogel stiffening. Blocking cell-mediated hydrogel degradation abolished stiffening, demonstrating that matrix metalloproteinase (MMP)-mediated remodeling is required for stiffening to occur. These results highlight the dynamic reciprocity between cells and their mechanical microenvironment during capillary morphogenesis and provide important insights for the rational design of materials for vasculogenic applications.
对于支持广泛临床应用的强大新血管生成的生物材料存在迫切需求。在这里，我们报告了细胞如何在聚乙二醇（PEG）基水凝胶内的内皮-基质细胞共培养模型中改变组织水平的机械性能。培养一周后，我们观察到初始性质非常软的水凝胶有明显的变硬。然而，单独的内皮细胞或基质细胞均不能诱导水凝胶变硬。这种变硬与血管形成的程度密切相关，但与水凝胶的压实或细胞增殖无关。尽管在 PEG 水凝胶内缺乏纤维状结构，但细胞产生的收缩力对于水凝胶变硬至关重要。α平滑肌肌动蛋白和胶原蛋白-1的上调也与增强的血管形成和水凝胶变硬相关。阻断细胞介导的水凝胶降解会消除变硬，表明基质金属蛋白酶（MMP）介导的重塑对于变硬的发生是必需的。这些结果突出了在毛细血管形态发生过程中细胞与其机械微环境之间的动态相互作用，并为血管生成应用的材料合理设计提供了重要的见解。
