A Single‐Component Adhesive Sponge Based on Blood‐Triggered and Autopenetrative Adhesion for Robust Vascular Closure

Abstract Achieving strong adhesion under wet and bleeding conditions remains a major challenge for medical adhesives. Existing strategies that utilize polymer chain penetration to overcome this have shown promise but typically rely on complex external stimuli, limiting clinical use. Here, MonoSeal is introduced, a body‐fluid‐triggered adhesive sponge composed of a single oxidized polysaccharide, operating via a newly proposed mechanism termed Autopenetrative Adhesion (APA). Unlike conventional approaches, APA enables spontaneous polymer chain penetration into moist tissues via concentration‐gradient‐driven diffusion, without any external activation. This self‐driven penetration dramatically increases the interfacial density and depth of reactive groups, which then form covalent bonds with tissue amines, establishing strong tissue anchoring. Meanwhile, the proteins present in body fluids serve to cross‐link the sponge matrix, forming a rapid in situ barrier that mechanically seals the wound. By tailoring the molecular weight and sponge architecture, the dissolution–cross‐linking kinetics is fine‐tuned to optimize adhesive penetration and mechanical sealing. The resulting MonoSeal achieved robust tissue adhesion and effectively sealed the 12 Fr puncture wound on the porcine femoral artery within 30 s. When delivered via a customized applicator, MonoSeal also demonstrates promising performance as a vascular closure device following interventional access in the porcine carotid artery.