Hirofumi Saito

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.

In vivo evaluation of bonding ability and biocompatibility of a novel biodegradable glue consisting of tartaric acid derivative and human serum albumin

We recently developed a novel biological glue from tartaric acid derivative (TAD) with two active ester groups and human serum albumin (HSA), named TAD-A. In this study, in vivo experiments were performed to investigate clinical applicability of TAD-A. TAD was prepared by reacting carboxyl groups of tartaric acid with N-hydroxysuccinimide in the presence of carbodiimide. Bonding strength was evaluated by using mouse skin closed with TAD-A of different TAD concentrations from 0.1 to 0.5 mmol in 0.8 mg of 44 w/w % HSA solution. Commercially available glues such as fibrin and aldehyde-based glue were used for comparison. We found that TAD-As bonding strength increased significantly with TAD-A concentration. The bonding strength of 0.5 mmol of TAD-A in 0.8 mg of 44 w/w % HSA solution was significantly higher than that of fibrin or aldehyde-based glue (p < 0.01), and that of 0.3 mmol of TAD-A was significantly higher than of fibrin glue (p < 0.05). To determine toxicity, we implanted disks made from TAD-A of different TAD concentrations from 0.1 to 0.5 mmol in 0.8 mg of 44 w/w % HSA solution subcutaneously in mice. The inflammatory reaction in surrounding tissue increased with increasing TAD concentration, and then the disks were absorbed. In conclusion, TAD-A has sufficient bonding strength and comparatively low toxicity in clinical use of 0.3 mmol or less of TAD and 0.8 mL of 44 w/w % HSA solution.

Development of Biocompatible Glues for Minimum Invasive Therapy

A biocompatible glue consisting of human serum albumin (HSA) and citric acid derivative (CAD), named CAD-A glue was developed. CAD was successfully synthesized by the reaction between citric acid and N-hydroxysuccinimide in the presence of 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride. When the CAD-A glue was applied to the collagenbased casings, it took 7 min to obtain half of maximum bonding strength (760 g/cm2). The bonding strength of this glue to collagen-based casings increased with increasing of HSA concentration.The bonding strength of CAD-A glue increased with increasing CAD concentration up to 200 mM, and then decreased with increasing CAD concentration under the fixed HSA concentration (50 w/w%). The CAD-A glue showed excellent wound closure ability rather than fibrin glue when applied to the mouse skin. These results suggested that this developed glue had both tissue compatibility and bonding strength for use in clinical field.