Biomimetic dual-functional hydrogel for pulmonary injury repair: Enhancing sealing and tissue regeneration.

Abstract

Pulmonary injuries resulting from surgical procedures or accidental trauma pose significant clinical challenges, frequently leading to complications such as air leakage, inflammation and abnormal tissue regeneration. Current therapeutic approaches remain inadequate to simultaneously prevent air leakage and facilitate effective pulmonary tissue regeneration. To address this, we developed a photocrosslinkable hydrogel, Lung-ma gel, derived from decellularized porcine lung extracellular matrix. Both in vitro and in vivo results showed that Lung-ma gel exhibits superior adhesive properties, enabling stable attachment to lung wound surfaces throughout respiratory cycles for effective sealing and prevention of air leakage. Moreover, Lung-ma gel preserves the inherent regenerative properties of the lung extracellular matrix, significantly enhancing epithelial cell proliferation, promoting angiogenesis, attenuating inflammatory responses and inhibiting fibrosis in injury sites, outperforming clinically used sealants, AA gel and fibrin gel. Transcriptomic analysis further revealed that Lung-ma gel specifically activates Wnt and Notch signaling pathways, orchestrating coordinated cascades for pulmonary angiogenesis and tissue regeneration. Collectively, Lung-ma gel is a novel dual-functional therapy that promote comprehensive pulmonary repair by combining effective mechanical sealing with functional tissue regeneration.