Halofuginone infused keratin hydrogel attenuates adhesions in a rodent cecal abrasion model.
BACKGROUND
Postoperative adhesion formation continues to be a significant surgical complication, and methods for preventing abdominopelvic adhesions remain limited. Halofuginone (HF) is a type-1 collagen synthesis inhibitor and may enhance the effects of a physical barrier in preventing adhesion formation. We evaluated the effectiveness of a HF infused keratin hydrogel on preventing adhesions in a rat cecal abrasion model.


METHODS
Laparotomy and standardized cecal abrasion was performed on 58 retired-breeder Sprague Dawley female rats to induce intra-abdominal adhesions. Rats were randomized to: no treatment; Interceed absorbable adhesion barrier; keratin hydrogel alone; or keratin hydrogel infused with 22 μg/mL of HF. Necropsies were performed at postop d-14 to assess the extent and tenacity of adhesions and grade histologic inflammation and fibrosis using a standard scoring system. Serum, liver, kidneys, and lungs were harvested to evaluate tissue HF concentrations. Protein and drug elution curves were generated to assess the release of HF from the hydrogel.


RESULTS
Treatment with Keratin-HF hydrogel resulted in significantly fewer abdominal adhesions than any other treatment, and significantly less dense adhesions compared with Interceed or keratin hydrogel alone. Subset histologic analysis did not reveal qualitative differences. HF was undetectable in serum and kidneys, and detected at negligible concentrations in liver and lungs. Keratin-HF hydrogel drug release in phosphate-buffered solution (PBS) was sustained over 7 d and correlated with keratin protein degradation.


CONCLUSIONS
Keratin-HF hydrogel is a novel therapeutic agent that may provide a better method for preventing the development of postoperative adhesions using a combined physical barrier and pharmacologic approached.
Department of Urology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA. cpeyton@wakehealth.edu
Charles C
CC
Peyton
Tristan
T
Keys
Seth
S
Tomblyn
David
D
Burmeister
Jan H
JH
Beumer
Juliane L
JL
Holleran
Joseph
J
Sirintrapun
Scott
S
Washburn
Steve J
SJ
Hodges
D000818:Animals; D002432:Cecum / Q000473:pathology* / Q000601:surgery; D005260:Female; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007633:Keratins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000737:chemistry*; D052999:Quinazolinones / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000517:prevention & control*
D010880:Piperidines; D052999:Quinazolinones; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007633:Keratins; C010176:halofuginone