Recent advances on in situ tissue adhesives

In situ tissue adhesives are emerging as promising alternatives to traditional surgical sutures and staples in irregular wound management and minimally invasive tissue repair. However, systematic summaries on in situ tissue adhesives are rarely reported. This review provides an overview of recent advances on in situ tissue adhesives based on adhesive coacervate glues, injectable hydrogels, and self-gelling powders. The focus is first on bioinspired adhesive coacervate glues mediated in situ tissue adhesion including recombinant proteins-based coacervate glues and synthetic coacervate glues, as well as curing of coacervate glues. Second, we present a detailed review of injectable hydrogel bioadhesives with different mechanisms starting with catechol chemistry, followed by chemical conjugation including Schiff base reaction, N-hydroxysuccinimide (NHS) ester/amine coupling reaction, click chemistry reactions, and boronic acid/cis-diol reaction. Photo-mediated in situ radical polymerization and noncovalent bonding-driven phase separation are also included. We then describe design strategies for in situ tissue adhesion mediated by synthetic and natural-derived self-gelling powder. Finally, the remaining challenges and future research directions of in situ tissue adhesives are discussed.