Tissue adhesive, rapid forming, and sprayable ECM hydrogel via recombinant tyrosinase crosslinking

We report on a tissue adhesive hydrogel based on novel recombinant tyrosinase mediated crosslinking. The adhesive hydrogels were fabricated by the site-directed coupling of tyramine-conjugated hyaluronic acid (HA_t, 1% w/v) and gelatin (3% w/v) (HG_gel) with novel tyrosinase derived from Streptomyces avermitilis (SA_Ty). The enzyme-based crosslinking by SA_Ty was fast, with less than 50 s for complete gelation, and the SA_Ty based crosslinking enhanced the physical properties and adhesive strength of the hydrogel significantly with the native tissue samples. Furthermore, by optimizing the injection conditions, we tailored the enzyme-based crosslinking hydrogels to be injectable and sprayable with a medical syringe and commercial airbrush nozzle, respectively. An in vivo analysis of the adhesive hydrogel showed a negligible immune reaction. In this study, demonstrate that the novel enzyme-based crosslinking hydrogel has a robust potential in tissue engineering and regenerative medicine.