Sprayable asymmetric hydrogel prevents postoperative pleural adhesions via physical and biological dual therapy.

Postoperative pleural adhesions represent a prevalent complication that causes chronic pain, impaired pulmonary function, and escalated reoperation risks. Current preventions strategies remain limited by inadequate multifunctionality and an underestimated fibro-inflammatory microenvironment. Here, we report a powder-based asymmetric adhesive hydrogel integrated with dual-drug liposomes for adhesion prophylaxis. Upon contact with body fluids, the powder rapidly forms an asymmetric adhesive hydrogel within 20 s, exhibiting strong wet-tissue adhesion (∼26 kPa), effective hemostasis, sealing, antibacterial and ROS scavenging capabilities, which display superiority over the commercial absorbable adhesion barrier (INTERCEED®). Embedded liposomes co-loaded with miR-124-3p (an identified critical miRNA from adhesive tissues) and simvastatin enable sustained release, synergistically disrupting the fibro-inflammatory cascade-miR-124-3p attenuates fibrosis via targeting TGFBR1 while simvastatin suppresses pro-inflammatory signaling. In pleural injury rats, the system markedly reduces adhesion, inflammation and fibrosis, while promoting alveolar repair. This study combines an easy-to-apply hydrogel with rationally designed combination therapy, offering a promising strategy for preventing postoperative adhesions with broad potential for translation to other fibrotic disorders.