Ultrasound-activated trilayer piezoelectric bio-adhesive for rapid repair and antibacterial treatment of gastrointestinal perforation.

Abstract

Gastrointestinal perforation (GIP) represents a critical abdominal emergency, the management of which hinges on prompt closure of the perforation and effective infection control. Currently, the application of biomaterials in the repair of acute GIP primarily focuses on rapid sealing and tissue repair, while still exhibiting certain limitations in antibacterial efficacy. To address this limitation, we developed a trilayer piezoelectric bio-adhesive consisting of an antibacterial piezoelectric layer, a conductive adhesive layer, and a a tissue-regenerative layer. The polyhydroxybutyrate (PHB) piezoelectric membrane loaded with silver-doped graphene oxide (Ag@GO) nanosheets, as the outermost layer, could generate the piezoelectric signals under ultrasound treatment, which were transmitted to the surrounding wound area through a tissue-adhesive poly(3-amino-4-methoxybenzoic acid)-gelatin (PAMB-G) hydrogel. Simultaneously, the innermost layer, prepared using a decellularized extracellular matrix (dECM) scaffold, provides a favorable microenvironment for tissue repair and vascular regeneration. <i>In vitro</i> experiments demonstrated that piezoelectric stimulation has dual functionality, facilitating tissue repair and exerting antibacterial effects, mainly because piezoelectric effects mediate Piezo1-dependent calcium influx, which promotes fibroblast activity and macrophage immunomodulation. <i>In vivo</i> experimental results demonstrated that under ultrasound (US) activation, this designed trilayer bio-adhesive achieved full-thickness healing within 15 days in rat models of gastric and small intestinal perforation. Furthermore, the bio-adhesive reduced the intraperitoneal bacterial burden in a cecal ligation and puncture (CLP) model and maintained stable leakage prevention and favorable tissue-healing capability in a pancreatic fistula model. This study presents an ultrasound-responsive trilayer piezoelectric biomaterial with rapid sealing, synergistic antibacterial activity, and tissue repair-promoting capabilities, offering a novel strategy and potential approach for treating gastrointestinal perforations.