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.