Unusual degradation behavior of citric acid-crosslinked gelatin in vitro and in vivo

The aim of this study was to evaluate the biodegradability and biocompatibility of gelatin matrices designed for drug-eluting stents (DESs). The matrices were prepared by crosslinking alkali-treated gelatin (AlGelatin) with a citric acid-based crosslinker, trisuccinimidyl citrate (TSC), to form AlGelatin-TSC. The biodegradation behavior of the matrices was evaluated in vitro and in vivo. An in vitro enzymatic degradation test showed that AlGelatin-TSC prepared at a TSC concentration of 20 mM is the most stable in collagenase solution compared to AlGelatin-TSC prepared at TSC concentrations higher or lower than 20 mM. Then, AlGelatin-TSC were implanted subcutaneously in rats to evaluate their biodegradability and tissue reaction in vivo. Similar to the in vitro degradation behavior, AlGelatin-TSC with TSC concentration of 20 mM exhibited the lowest biodegradable rate in vivo among all AlGelatin-TSC. In addition, strong inflammation and calcification were not observed for AlGelatin-TSC at any TSC concentration. From an analysis of the crosslinking density of the resulting AlGelatin-TSC, the lowest biodegradability of AlGelatin-TSC with TSC concentration of 20 mM was due to the highest crosslinking density of the matrix. These results suggest that AlGelatin-TSC is suitable for use as matrices in DESs because of its excellent biocompatibility and biodegradability.