Biodegradable Adhesives Composed of Human Serum Albumin and Organic Acid-based Crosslinkers with Active Ester Groups

The organic acid-based crosslinkers trisuccinimidyl citrate (TSC), disuccinimidyl malate (DSM), and disuccinimidyl tartarate (DST) were combined with human serum albumin (HSA) to produce biodegradable solid— liquid-type adhesives, TSC-A, DSM-A, and DST-A. The bonding time of TSC-A, DSM-A, and DST-A was 15, 10, and 5 min, respectively, when the content of organic acid-based crosslinkers was 0.5 mmol and the HSA concentration was 44 w/v%. Five minutes after application of the adhesives, the DST-A adhesive had the greatest bonding strength (489.14 ± 93.06 kPa) compared with TSC-A (120.86 ± 73.83 kPa) and DSM-A (224.44 ± 79.53 kPa). The bonding strength of DSM-A and DST-A increased with increasing DSM or DST content up to 0.5 mmol, after that the bonding strength decreased. While, the bonding strength of the TSC-A adhesive was relatively low at any TSC content compared with the other adhesives. The bonding strength of DST-A with 0.3 mmol of DST increased with increasing HSA concentration up to 44 w/v%, and then decreased. The bonding strength of the DST-A adhesive was 3.2-fold greater than that of a commercial aldehyde-based adhesive and 6-fold greater than that of a fibrin-based adhesive. DST-A has excellent biocompatibility, bioabsorbability, and only mild tissue reaction in rat subcutaneous tissues.