Abstract
Postoperative peritoneal adhesions cause pelvic pain, infertility, and potentially lethal bowel obstruction. We have designed and synthesized injectable hydrogels that are formed by mixing hydrazide-modified hyaluronic acid (HA) with aldehyde-modified versions of cellulose derivatives such as carboxymethylcellulose (CMC), hydroxypropylmethyl cellulose (HPMC), and methyl cellulose (MC). Hydrogels degraded in the presence of hyaluronidase in vitro, with HA-MC and HA-HPMC degrading more slowly than HAX and HA-CMC. All the cellulose-derived gels showed efficacy in reducing the area of adhesion formation in a rabbit sidewall defect-bowel abrasion model. In addition, we have designed and synthesized an injectable hydrogel composed of cross-linkable modified hyaluronic acids conjugated to dexamethasone, and investigated its anti-inflammatory function. The hydrogel degraded in media over 5 days, releasing dexamethasone slowly over that time preventing TNF-α production from lipopolysaccharide-stimulated primary mousice macrophages in vitro. Further research is on-going. We are designing cisplatin releasing system based on this in-situ crosslinkable hydrogel system for treating peritoneal dissemination.
