In vitro microbial inhibition, bonding strength, and cellular response to novel gelatin-alginate antibiotic-releasing soft tissue adhesives

Tissue bioadhesives have raised interest in the last few decades as an alternative to sutures or staples in wound closing applications because of various advantages. They are less time consuming, less painful, and can be less expensive, without compromising the cosmetic outcome. Even though extensive efforts have been made, an ideal tissue adhesive has not been developed to date, mostly because of toxicity or weak bonding strength issues. Novel bioadhesives comprised gelatin and alginate with carbodiimide (N-ethyl-N-(3-dimethylaminopropyl) carbodiimide [EDC]) as the cross-linking agent were recently developed by our research group. In the current research, N-hydroxysuccinimide (NHS) was added to the cross-linking reaction to enable a decrease in the EDC content and therefore also the cytotoxicity, without decreasing the bonding strength. The antibiotic drug clindamycin was added to the bioadhesive formulation. It was selected because of being inert toward the cross-linking reaction. The effects of EDC, NHS, and clindamycin concentrations on the ex vivo bonding strength, drug release profile, and fibroblast viability, as well as the microbial inhibition, were studied. Incorporation of clindamycin was found to improve the bonding strength of the adhesive. Its release profile was highly effective against the two relevant bacterial strains, Staphylococcus albus and Staphylococcus aureus, which were eradicated within less than 48h. The good cytotoxicity results indicate that our new antibiotic-eluting bioadhesives represent an effective and selective treatment option for bacterial infections. Delivering an antibiotic drug locally using our bioadhesive could decrease the risk of infections and increase the therapeutic effect of the bioadhesive itself.