Biocompatible high-strength glue consisting of citric acid derivative and collagen

A novel CAD–C glue consisting of collagen and citric acid derivative (CAD) was developed. CAD works as a crosslinking reagent of collagen. We prepared CAD by modifying three carboxyl groups of citric acid with N-hydroxysuccinimide in the presence of 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride. Bonding of this glue to collagen casings increased up to a CAD concentration of 100 mM, then decreased, becoming 50% of the maximum within 5 min, then increased with time and saturated within 10 min. The maximum bonding strength of this glue was 11 times higher than that of fibrin-based glue and similar to that of aldehyde-based glue. Excellent biocompatibility and resorbability were observed even after its subcutaneous injection into the backs of mice, indicating its applicability as a soft-tissue-bonding reagent.