Injectable Click Chemistry-Based Bioadhesives for Accelerated Wound Closure

Abstract

Tissue adhesives play a vital role in surgical process as a substitution of sutures for wound closure. However, most currently existing tissue adhesives suffer cell toxicity, weak adhesive strength to tissue, and costly. Herein, by taking advantage of the fast and specific inverse-demand Diels-Alder cycloaddition reaction, a series of bioadhesive were produced by employing copper-free click chemistry pair trans-cyclooctene (TCO) /tetrazine (Tz) in the chitosan. The gelation time of the bioadhesives can be optimized to be less than 2 minutes, which meets the need for surgical wound closure in practice. With the adding of 4-arm polyethylene glycol propionaldehyde (PEG-PALD) as a co-crosslinker, the adhesive strength of the bioadhesives is optimized to be 2.7 times higher than that of the conventional fibrin glue. Moreover, by adjusting the amount of the co-crosslinker, the swelling ratio and pore size of the chitosan bioadhesives can be tuned to fit the need of drug encapsulation and cell seeding. The chitosan bioadhesives possess excellent in vitro cytocompatibility. Through a mice skin incision wound model, we proved that the chitosan bioadhesives was able to close the wound faster and promote wound healing process faster than the fibrin glue. In conclusion, our results support that the innovative click-chemistry based bioadhesives have been developed with improved physical and biological properties for surgical wound closures.