title: Halofuginone inhibits collagen deposition in fibrous capsules around implants.
abstract: Fibrous capsule formation around implants remains a difficult problem that has been studied for decades. The etiology is elusive, but the end result is the deposition of a dense collagenous capsule around implanted materials. The purpose of this study was to determine the effects of a type I collagen synthesis inhibitor, halofuginone, on fibrous capsule formation around implanted materials. Silastic disks were implanted subcutaneously into 4 groups of adult male rats for up to 8 weeks. Group 1 received drug throughout the study, group 2 received drug during the first half only, group 3 received drug during the second half only, and the control group received no drug. Implants were removed and histology of the capsules was examined. A collagen index score was calculated from digital images of trichrome-stained histologic sections, which permitted semiquantitative comparison of collagen content among the 4 groups. The collagen index values clearly indicate that halofuginone effectively inhibited collagen deposition within the capsule around the implanted disks. Halofuginone treatment also resulted in a decrease in the collagen index score in rat skin, indicating that halofuginone may affect preexisting collagenous structures. The ability of halofuginone to inhibit collagen deposition in new and preexisting fibrous capsules suggests that it may be a useful adjunct to minimize the formation of capsules around implantable prostheses.
authors.affiliation: Division of Plastic, Reconstructive, Maxillofacial, and Oral Surgery, Duke University Medical Center, Durham, NC 27710, USA. kevin.olbrich@duke.edu
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Olbrich
authors.forename: Ricardo
authors.initials: R
authors.lastname: Meade
authors.forename: William
authors.initials: W
authors.lastname: Bruno
authors.forename: Lior
authors.initials: L
authors.lastname: Heller
authors.forename: Bruce
authors.initials: B
authors.lastname: Klitzman
authors.forename: L Scott
authors.initials: LS
authors.lastname: Levin
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D003124:Colorimetry; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D010880:Piperidines; D019736:Prostheses and Implants / Q000009:adverse effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D052999:Quinazolinones; D051381:Rats; D017207:Rats, Sprague-Dawley; D012826:Silicone Elastomers / Q000009:adverse effects; D040521:Subcutaneous Tissue / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D010880:Piperidines; D011500:Protein Synthesis Inhibitors; D011799:Quinazolines; D052999:Quinazolinones; D012826:Silicone Elastomers; D016212:Transforming Growth Factor beta; C010176:halofuginone