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.


METHODS
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.


METHODS
University animal research facility.


METHODS
Female Wistar rats.


METHODS
Injuries (3 x 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.


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


RESULTS
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.


CONCLUSIONS
Mitomycin C-loaded crosslinked HA films and gels reduced formation of postoperative intraperitoneal adhesions.
Liu
Yanchun
Y
Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Salt Lake City, UT 84108, USA.
Li
Hao
H
Shu
Xiao Zheng
XZ
Gray
Steven D
SD
Prestwich
Glenn D
GD
D000005:Abdomen / Q000601:surgery; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020100:Hydrogels / Q000494:pharmacology*; D016685:Mitomycin / Q000494:pharmacology*; D011183:Postoperative Complications / Q000188:drug therapy / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D000267:Tissue Adhesions / Q000188:drug therapy / Q000517:prevention & control*; D014599:Uterus / Q000601:surgery
D000276:Adjuvants, Immunologic; D003432:Cross-Linking Reagents; D004338:Drug Combinations; D020100:Hydrogels; D016685:Mitomycin; D006820:Hyaluronic Acid