Prevention of Peritoneal Adhesions by Ferric Ion-Cross-Linked Hydrogels of Hyaluronic Acid Modified with Iminodiacetic Acids

We fabricated ferric ion-cross-linked hydrogels of a chelating hyaluronic acid (HA) derivative. HA was conjugated with iminodiacetic acid (IDA) at 22% of a modification degree to its disaccharide unit of HA. This conjugate (HA–IDA) showed degradability by hyaluronidase even after the IDA modification, and its degradation rate was almost the same as that of HA. HA–IDA and HA formed hydrogels (FeHA and FeHA–IDA) by cross-linking with ferric ions (Fe3+). The storage modulus of FeHA–IDA was ca. 100 Pa, which was higher than ca. 10 Pa of FeHA. FeHA–IDA showed excellent biocompatibility to a mesothelium cell line as well as rapid degradation. Above all, FeHA–IDA showed efficacy in reducing adhesion formation in a rat sidewall defect-bowel abrasion model.