Human gelatin tissue-adhesive hydrogels prepared by enzyme-mediated biosynthesis of DOPA and Fe3+ion crosslinking

Abstract

Gelatin is extensively used as a biomaterial for diverse pharmaceutical and medical applications due to its excellent biocompatibility and biodegradability. Here we present bio-inspired tissue-adhesive gelatin hydrogels prepared by the enzyme-mediated synthesis of L-3,4-dihydroxyphenylalanine (L-DOPA) and Fe3+ ion crosslinking. Gelatin of human origin was obtained through two major steps, extracellular matrix (ECM) extraction from human adipose tissue and gelatin isolation from the ECM. The tyrosine residues in human gelatin were converted into DOPA by enzymatic reaction with tyrosinase. Upon the addition of Fe3+ ions, the DOPA-modified gelatin formed a sticky hydrogel within seconds through complexation between the DOPA molecules and Fe3+ ions. The final DOPA-modified, Fe3+ ion-crosslinked gelatin hydrogels retained their hydrogel stability well at body temperature in an aqueous environment and exhibited appropriate mechanical properties. The hemostatic ability of the DOPA–Fe3+ gelatin hydrogels was explored using a hemorrhaging liver rat model. Shortly after the injection of the DOPA–Fe3+ gelatin hydrogel, the bleeding was arrested in the hemorrhaging site of the liver. Overall results suggest that the DOPA–Fe3+ gelatin hydrogel, with its good elastic and hemostatic properties, is a promising tissue adhesive for use in a wide variety of surgical operations.