Bonding of soft tissues using a novel tissue adhesive consisting of a citric acid derivative and collagen

A novel tissue adhesive consisting of collagen and citric acid derivative (CAD) was developed. In this adhesive, CAD works as a cross-linking reagent of collagen. CAD was prepared by modifying three carboxyl groups of citric acid with N-hydroxysuccinimide in the presence of 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride. From 1H-NMR spectrum, three active ester groups were introduced into one citric acid molecule with a high yield, exceeding 80%. The bonding strength of this tissue adhesive to porcine soft tissue increased with increasing CAD and collagen concentration. The maximum bonding strength of this adhesive was similar to the roughly 80% tear strength of the original soft tissue. The IC50 of CAD for the L929 fibroblast was 10 times less cytotoxic than was that of the glutaraldehyde and formaldehyde used in aldehyde-based adhesive. This adhesive had biodegraded under the skin of mice within 7 days after subcutaneous injection. These results suggest that this newly developed adhesive is applicable as a bonding reagent for soft tissue.