Mechanically Tunable Poly(Ethylene Glycol) Diacrylate Hydrogels Reveal Stiffness-Related Impairments in Capillary Sprouting in Experimental Lung Fibrosis

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2025-07-17 DOI:10.1111/micc.70018

Julie Leonard-Duke, Samuel M. J. Agro, David J. Csordas, Riley T. Hannan, Anthony C. Bruce, Jeffrey M. Sturek, Shayn M. Peirce, Lakeshia J. Taite

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Abstract

Objective

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.

Methods

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.

Results

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.

Conclusions

Our results suggest a compensation in vasculature derived from fibrotic tissue to matrix mechanics in promoting angiogenic sprouting.

Abstract Image

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机械可调聚乙二醇二丙烯酸酯水凝胶揭示实验性肺纤维化中毛细血管发芽的硬度相关损伤

支持3D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，导致细胞外基质（ECM）的机械硬化。为了研究ECM的机械刚度如何影响微血管重塑，我们开发了一种具有生物活性的聚乙二醇二丙烯酸酯（PEGDA）水凝胶模型，其刚度可调，允许微血管发芽。方法采用PEGDA水凝胶体外培养健康小鼠和纤维化小鼠肺组织7 d。通过影像学和分泌血管生成标志物评估肺段毛细血管发芽。结果健康肺外植体在较硬的水凝胶上芽的形成和长度减少。然而，来自纤维化肺外植体的芽不受水凝胶硬度的影响。这种差异与纤维化肺外植体中血管生成标志物和基质重塑酶的高表达有关。结论我们的研究结果表明，在促进血管生成芽的过程中，来自纤维化组织的血管系统对基质力学有一定的补偿作用。

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来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.