Microcirculation (New York, N.Y. : 1994) · 2025
Mechanically Tunable Poly(Ethylene Glycol) Diacrylate Hydrogels Reveal Stiffness-Related Impairments in Capillary Sprouting in Experimental Lung Fibrosis.
СтатьяПоддержка правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.
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.