Prevention of postoperative peritoneal adhesions in rats with sidewall defect-bowel abrasions using metal ion-crosslinked N-succinyl chitosan hydrogels

Abstract In situ injectable hydrogels have attracted much attention as adhesion barriers. In this study, N-succinyl chitosan (CH-Su) hydrogels were crosslinked with various polyvalent metal ions (Fe3+, Al3+, and Ca2+) and were developed for the prevention of peritoneal adhesions. CH-Su hydrogels crosslinked with Fe3+ (CH-Su/Fe3+) or Al3+ (CH-Su/Al3+) indicated higher Young's modulus, longer degradation times, and shorter gelation times compared with those crosslinked with Ca2+ (CH-Su/Ca2+). In addition, CH-Su/Fe3+ hydrogels had higher Young's modulus than CH-Su/Al3+ hydrogels, likely reflecting differences in stability constants between CH-Su and each ion. Although while CH-Su/Al3+ and CH-Su/Ca2+ hydrogels were not significantly cytotoxic in cell viability assays, CH-Su/Fe3+ hydrogels showed significantly higher cytotoxicity than controls, presumably due to the release of Fe3+ and decreases in pH. Consistent with the ion-dependent hydrogel properties above, CH-Su/Al3+ hydrogels showed the highest anti-adhesive effects, and significantly decreased adhesion scores in a rat model of sidewall defect-bowel abrasion.