Leonard-Duke Julie, Agro Samuel M J, Csordas David J, Hannan Riley T, Bruce Anthony C, Sturek Jeffrey M, Peirce Shayn M, Taite Lakeshia J
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA.
Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, USA.
Microcirculation. 2025 Jul;32(5):e70018. doi: 10.1111/micc.70018.
Synthetic hydrogels that support 3D cell culture are widely used as platforms for modeling disease, such as tissue fibrosis, which leads to mechanical stiffening of the extracellular matrix (ECM). To interrogate how mechanical stiffness of the ECM affects microvascular remodeling, we developed a bioactive poly(ethylene glycol) diacrylate (PEGDA) hydrogel model with tunable stiffness that permits microvascular sprouting.
Lung explants harvested from healthy and fibrotic mice were cultured ex vivo on PEGDA hydrogels for 7 days. Capillary sprouting from lung segments was evaluated via imaging and secreted angiogenic markers.
Healthy lung explants had decreased sprout formation and length on stiffer hydrogels. The sprouts from fibrotic lung explants, however, were not impacted by hydrogel stiffness. This difference was associated with higher expression of angiogenic markers and matrix remodeling enzymes in the fibrotic lung explants.
Our results suggest a compensation in vasculature derived from fibrotic tissue to matrix mechanics in promoting angiogenic sprouting.
支持三维细胞培养的合成水凝胶被广泛用作疾病建模平台，如组织纤维化，其会导致细胞外基质（ECM）机械硬化。为了探究ECM的机械硬度如何影响微血管重塑，我们开发了一种具有可调硬度的生物活性聚（乙二醇）二丙烯酸酯（PEGDA）水凝胶模型，该模型允许微血管发芽。
从健康和纤维化小鼠体内获取的肺组织外植体在PEGDA水凝胶上进行7天的体外培养。通过成像和分泌的血管生成标志物评估肺段的毛细血管发芽情况。
健康的肺组织外植体在较硬的水凝胶上发芽形成减少且芽长度变短。然而，纤维化肺组织外植体的芽不受水凝胶硬度的影响。这种差异与纤维化肺组织外植体中血管生成标志物和基质重塑酶的高表达有关。
我们的结果表明，在促进血管生成发芽方面，纤维化组织来源的血管系统对基质力学存在一种补偿作用。
