title: Local delivery of nicotine does not mitigate fibrosis but may lead to angiogenesis.
abstract: As with most implanted biomaterials, the wound healing response following implantation of a silicone breast implant leads to the formation of a fibrotic capsule. This can result in capsular contracture, a painful complication that often necessitates the removal of implant. It is well established that nicotine and nicotinic agonists inhibit inflammatory signaling. Based on the link between the inflammatory response and capsule formation, we hypothesized that local delivery of nicotine from the implant may lead to the reduction in inflammation and capsule thickness, which may ultimately reduce the incidence of capsular contracture. Nicotine was loaded into PDMS membranes using a previously established method. The loaded materials were implanted into the submammary pockets between the third and fourth mammary glands of rats. To confirm that the nicotine was acting locally and not systemically, serum cotinine, the primary metabolite of nicotine, was measured by ELISA at 3 days. Thirty days post implantation, the animals were euthanized and the tissue samples were fixed for histological analysis. Blood vessel density was measured immunohistochemically, while the capsule thickness was evaluated microscopically. While the presence of the nicotine metabolite, cotinine, in the serum at the early time points demonstrated that the nicotine was released locally from the devices, there were no significant differences in the capsule thickness between the control and experimental implants. However, the results indicated that there were differences in angiogenesis with the local delivery of nicotine, which may have other implications for the development of biomaterials.
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University Hamilton Ontario, Canada.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Ng
authors.forename: Neven
authors.initials: N
authors.lastname: Awad
authors.forename: Michael A
authors.initials: MA
authors.lastname: Brook
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
authors.forename: Heather
authors.initials: H
authors.lastname: Sheardown
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D018427:Breast Implants / Q000009:adverse effects*; D004343:Drug Implants; D005260:Female; D005355:Fibrosis; D006801:Humans; D057910:Implant Capsular Contracture / Q000473:pathology / Q000517:prevention & control; D008321:Mammary Glands, Animal / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D008422:Materials Testing; D023421:Models, Animal; D009389:Neovascularization, Pathologic / Q000209:etiology; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012826:Silicone Elastomers; D013499:Surface Properties; D014945:Wound Healing / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D004343:Drug Implants; D012826:Silicone Elastomers; D009538:Nicotine