Self-adhesive small intestinal submucosa-based hydrogel patch with dual-stage sequential curcumin release for pulmonary air leak sealing, sustained anti-inflammatory modulation, and lung regeneration

Developed a dual-stage sequential curcumin releasing SIS-based self-adhesive hydrogel lung patch. • Achieved strong wet adhesion, suture-free air-leak sealing, and staged anti-inflammatory therapy. • Validated reduced pneumothorax, fibrosis, and inflammatory pleural adhesions in rat and pig pulmonary injury repair models. Postoperative pulmonary air leakage and uncontrolled inflammation remain major challenges after lung resection, while existing patches primarily provide mechanical sealing without active regulation of the healing microenvironment. Here, we report a self-adhesive, dual-stage sequential drug-releasing lung patch (Hydrogel patch–Cur) that integrates rapid sealing with stage-specific immunomodulation. The patch is constructed by coating a decellularized porcine small intestinal submucosa (SIS) scaffold with a bilayer gelma-based hydrogel system, enabling sequential curcumin (Cur) delivery through structurally distinct networks. The outer low-crosslinked gelma30–CS layer enables rapid drug release and enhanced wet-tissue adhesion, while the inner highly crosslinked gelma80 layer provides sustained release for prolonged immune regulation. This design establishes a time-dependent therapeutic profile that matches the dynamic inflammatory phases of lung repair. The patch exhibits strong adhesion (32-fold higher adhesion than uncoated SIS) on wet tissues and effective sealing performance without the need for sutures or staples. In vitro studies demonstrate promoted macrophage polarization toward a pro-regenerative phenotype and significant suppression of pro-inflammatory cytokines. In vivo, the patch rapidly prevents air leakage and pneumothorax, reduces inflammation and fibrosis, and accelerates lung tissue regeneration in both rat and porcine models, outperforming conventional methods and a clinically used self-adhesive patch. This study presents a clinically translatable strategy that combines self-adhesive sealing with gradient drug delivery for improved postoperative lung repair.