It has been a great challenge to develop aldehyde-free tissue adhesives that can function rapidly and controllably

on wet internal tissues with fine adhesion strength, sound biocompatibility and degradability.

To this end, we have devised a mussel-inspired easy-to-use double-crosslink tissue adhesive (DCTA)

comprising a dopamine-conjugated gelatin macromer, a rapid crosslinker (namely, Fe3+), and a longterm

acting crosslinker (namely, genipin). As a mussel-inspired gluing macromer, dopamine is grafted

onto gelatin backbone via an one-step reaction, the catechol groups of which are capable of performing

strong wet adhesion on tissue surfaces. By addition of genipin and Fe3+, the formation of catechol–Fe3+

complexation and accompanying spontaneous curing of genipin-primed covalent crosslinking of gluing

macromers in one pot endows DCTA with the double-crosslink adhesion mechanism. Namely, the reversible

catechol–Fe3+ crosslinking executes an controllable and instant adhesive curing; while genipininduced

stable covalent crosslinking promises it with long-term effectiveness. This novel DCTA exhibits

significantly higher wet tissue adhesion capability than the commercially available fibrin glue when

applied on wet porcine skin and cartilage. In addition, this DCTA also demonstrates fine elasticity, sound

biodegradability, and biocompatibility when contacting in vitro cultured cells and blood. In vivo biocompatibility

and biodegradability are checked and confirmed via trials of subcutaneous implantation in

nude mice model. This newly developed DCTA may be a highly promising product as a biological glue

for internal medical use including internal tissue adhesion, sealing, and hemostasis.