Sudden hemorrhage stemming from internal organ wounds poses a grave and potentially fatal risk if left untreated. Injectable-hydrogel-based tissue sealants featuring multiple actions, including fit-to-shape in-situ gelation, rapid hemostasis, pro-angiogenic, anti-bacterial and outcome tracking, are ideal for the management of organ trauma wounds. Herein, we have developed an injectable-hydrogel tissue sealant AN@CD-PEG&TQ which consists of 4-arm PEG-SC, AN@CD nanoprobe and two bioactive peptides (anti-microbial peptide Tet213 and pro-angiogenic peptide QK). Among them, AN@CD nanoparticles form through host/guest complexation of amino-group-containing β-cyclodextrin and adamantyl group, enabling in-situ biomarker (NO)-activatable optoacoustic/NIR-II fluorescent imaging. The ample -NH2 groups on the surface of AN@CD readily engage in rapid cross-linking with succinimidyl ester groups located at the ends of 4-arm PEG-SC. This cross-linking expedites the gelation process without necessitating additional initiators or cross-linking agents, thus significantly enhancing both hydrogel’s application convenience and biocompatibility. Bioactive peptides (Tet213 and QK) safeguard against possible bacterial infections and facilitate angiogenesis and eventually improve organ wounds healing. This hydrogel-based tissue sealant demonstrates superior therapeutic and bioimaging performance in various mouse models including liver hemorrhage, gastric perforation and bacterial-infected skin wound mouse models, highlighting its potential as a high-performance wound sealant for organ bleeding wound management.
