Effect of additives on gelation and tissue adhesion of gelatin-poly(L-glutamic acid) mixture

Gelation and tissue adhesion of mixtures of gelatin and poly (L-glutamic acid) (PLGA) aqueous solution were investigated in the presence of additives following the addition of a water-soluble carbodiimide (WSC) that induced chemical cross linking between gelatin and PLGA. To prevent spontaneous gelation of the mixed solution through physical cross linking between gelatin molecules at room temperature, additives were added to the mixed solution. Among the additives studied, starch and urea were effective in preventing the spontaneous physical gelation. The mixed gelatin and PLGA solution set to a cross-linked hydrogel within scores of second by WSC addition, irrespective of the presence of urea, whereas the viscosity of the solution with added starch was too high to measure the gelation time. The cross-linked gelatin-PLGA hydrogels with and without urea showed higher bonding strength to soft tissues than fibrin glue. This was in marked contrast to gelatin-PLGA hydrogels with soluble starch. Irrespective of the presence of urea, the gelatin-PLGA hydrogels gradually biodegraded in the back subcutis of mice over 3 months and no severe inflammatory response to the hydrogels was observed. These findings indicate that urea is promising as an additive to prevent spontaneous physical gelation of the mixed gelatin and PLGA aqueous solution without changing the characteristics of WSC-induced cross linking and tissue adhesion of the formed hydrogel.