An injectable adhesive hydrogel based on N-hydroxysuccinimide γ-poly(glutamic acid) and 4-armed poly(ethylene glycol) amine showed rapid gelation time, strong mechanical strength, satisfactory burst pressure and excellent hemostatic performance.

Hemostatic powders are widely used in clinical and emergency situations but often exhibit low wet adhesion, cytotoxicity concerns, and do not work well for lethal non‐compressible hemorrhage. Here a new kind of gelable and adhesive powder (GAP) is developed, which integrates chitosan microspheres (CM), tetra‐armed poly(ethylene glycol) amine (Tetra‐PEG‐NH2), and tetra‐armed poly(ethylene glycol) succinimidyl succinate (Tetra‐PEG‐SS). Upon application to the wound site, the macroporous CM can rapidly absorb the interfacial liquids, and meanwhile, the hydrated GAP turns into hydrogel (crosslinking between Tetra‐PEG‐SS and CM/Tetra‐PEG‐NH2) with stable and robust adhesion to the wet tissue though covalent bonding. The in vitro and in vivo results suggest that the GAP with optimized formulation exhibits strong tissue adhesive, high burst pressure, and enhanced blood clotting ability, as well as excellent biocompatibility and on‐demand removal properties. A significantly improved hemostatic efficacy is demonstrated in the rat liver, spleen, and femoral artery injury models compared to that of the CM, commercial fibrin glue, and Yunnan Baiyao (YB). The GAP can also halt the severe bleeding from pig visceral organs. Overall, the proposed GAP has many advantages including good biocompatibility, rapid and effective hemostasis, low cost, and ease of use, making it as a promising hemostat for lethal non‐compressible hemorrhage control.

The development of injectable hydrogels with good biocompatibility, self-healing, and superior hemostatic properties is highly desirable in emergency and clinical applications. Herein, we report an in situ injectable and self-healing hemostatic hydrogel based on choline phosphoryl functionalized chitosan (CS-g-CP) and oxidized dextran (ODex). The CP groups were hypothesized to accelerate hemostasis by facilitating erythrocyte adhesion and aggregation. Our results reveal that the CS-g-CP/ODex hydrogels exhibit enhanced blood clotting and erythrocyte adhesion/aggregation capacities compared to those of the CS/ODex hydrogels. The CS-g-CP50/ODex75 hydrogel presents rapid gelation time, good mechanical strength and tissue adhesiveness, satisfactory bursting pressure, and favorable biocompatibility. The hemostatic ability of the CS-g-CP50/ODex75 hydrogel was significantly improved compared to that of the CS/ODex hydrogel and commercial fibrin sealant in the rat tail amputation and liver/spleen injury models. Our study highlights the positive and synergistic effects of CP groups on hemostasis and strongly supports the CS-g-CP50/ODex75 hydrogel as a promising adhesive for hemorrhage control.

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Comprehensive SummaryHydrogel bioadhesives represent promising and efficient alternatives to sutures or staples for gastrointestinal (GI) perforation management. However, several concerns remain for the existing bioadhesives including slow and/or weak adhesive, poor mechanical strength, low biocompatibility, and poor biodegradability, which largely limit their clinical applications in GI perforation repair. In this work, we introduce an in situ injectable Tetra‐PEG hydrogel bioadhesive (SS) composed of tetra‐armed poly(ethylene glycol) amine (Tetra‐PEG‐NH2) and tetra‐armed poly(ethylene glycol) succinimidyl succinate (Tetra‐PEG‐SS) for the sutureless repair of GI defects. The SS hydrogel exhibits rapid gelation behavior and high burst pressure and is capable of providing instant robust adhesion and fluid‐tight sealing in the ex vivo porcine intestinal and gastric models. Importantly, the succinyl ester linkers in the SS hydrogel endow the bioadhesive with suitable in vivo degradability to match the new GI tissue formation. The in vivo evaluation in the rat GI injured model further demonstrates the successful sutureless sealing and repair of the intestine and stomach by the SS hydrogel with the advantages of neglectable postsurgical adhesion, suppressed inflammation, and enhanced angiogenesis. Together, our results support potential clinical applications of the SS bioadhesive for the high‐efficient repair of GI perforation.This article is protected by copyright. All rights reserved.