Next-Generation Hydrogel Skin Adhesives: From Bioinspired Adhesion Chemistry to Regenerative Wound Interfaces

Hydrogel-based skin adhesives have emerged as promising alternatives to conventional wound-closure methods such as sutures and staples because they can establish conformal contact with soft, irregular, and wet tissue surfaces. Recent advances in polymer chemistry and biointerface engineering have enabled the development of hydrogel adhesives that combine strong wet adhesion with mechanical compliance, cytocompatibility, and therapeutic functionality. In this review, we summarize recent progress in the design of hydrogel-based skin adhesives, with particular emphasis on the chemical and interfacial mechanisms governing tissue adhesion, including covalent bonding, supramolecular interactions, and bioinspired polyphenol-mediated adhesion. We first outline key features of skin structure and wound healing that define the functional requirements of skin adhesives. We then discuss methods for evaluating adhesive performance, highlighting interfacial toughness and the need for standardized testing under clinically relevant conditions. Emerging strategies for on-demand debonding that enable atraumatic removal after wound closure are also reviewed. In addition, we examine key biological design considerations, including cytocompatibility, immune regulation, angiogenesis, and antibacterial activity. Finally, we highlight current challenges and future opportunities for multifunctional hydrogel adhesive that not only close wounds but also actively support tissue repair and regeneration.