Crosslinked hyaluronan hydrogels containing mitomycin C reduce postoperative abdominal adhesions

Objective

To evaluate the efficacy of crosslinked hyaluronan (HA) hydrogels that contained covalently-bound mitomycin C (MMC) in reducing postoperative adhesions in a rat uterine horn model.

Design

Two independent parameters were investigated: [1] the quantity of MMC in preformed crosslinked hydrogel films and [2] the efficacy of intraperitoneal injection of in situ crosslinkable solutions.

Setting

University animal research facility.

Animal(s)

Female Wistar rats.

Intervention(s)

Injuries (3 × 10 mm) were made to contacting serosal surfaces of the medial uterine wall musculature in female rats. Two treatment protocols were used. In the first, sterile crosslinked HA films that contained different MMC loadings (0, 0.5%, and 2%) were applied to two injured uterine horns; control animals received no films. In the second protocol, MMC-loaded crosslinked HA gels that contained different MMC loadings (0.31%, 0.625%, and 1.25%) were spread on the site of uterine horn injury (1 mL); then, an additional 4 mL of the same formulation was injected into the peritoneal cavity after abdominal closure. Control animals were injected with 5 mL of buffer only.

Main Outcome Measure(s)

Extent of postoperative adhesions between uterine horns and with surrounding tissues and organs.

Result(s)

Mitomycin C–loaded crosslinked HA films and in situ crosslinked gels were more effective in reducing postoperative adhesion formation than were buffer controls or crosslinked HA films without MMC.

Conclusion(s)

Mitomycin C–loaded crosslinked HA films and gels reduced formation of postoperative intraperitoneal adhesions.

Key Words:  Controlled release , antiproliferative drug , rat uterine horn , postsurgical adhesion prevention , glycosaminoglycan , polyethyleneglycol crosslinker , conjugate addition , thiol-reactive group