title: Local inhibition of angiogenesis by halofuginone coated silicone materials.
abstract: Anti-angiogenic therapy is a promising approach for the treatment of increased angiogenesis in certain diseases. We aimed to investigate the local anti-angiogenic effect of silicone implants coated with Halofuginone, an angiogenesis inhibitor that inhibits synthesis of collagen-type-I and matrix metalloproteinases. The degree of angiogenesis was observed after implantation of surface modified Halofuginone eluting silicone implants into a submuscular pocket in rats over a period of 3 months. Subsequently, key mediators of angiogenesis (TGF-beta-1, bFGF, COL1A1, MMP-2, MMP-9, VEGF and PDGF) were established by immunohistological staining and RT-PCR and statistically evaluated. In comparison to uncoated silicone implants, Halofuginone eluting silicone implants lead to a significant local decrease of angiogenesis. Halofuginone eluting hybrid surface silicone implants have a significant local anti-angiogenic effect by down-regulating the expression activity of key mediators of angiogenesis.
authors.affiliation: Department of Orthopaedic Surgery, König-Ludwig-Haus, Julius-Maximilians-University Würzburg, Brettreichstr. 11, 97074 Würzburg, Germany. m-jordan.klh@uni-wuerzburg.de
authors.forename: Martin C
authors.initials: MC
authors.lastname: Jordan
authors.forename: Philip H
authors.initials: PH
authors.lastname: Zeplin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation / Q000187:drug effects; D008422:Materials Testing; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D019736:Prostheses and Implants; D052999:Quinazolinones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012828:Silicones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D020099:Coated Materials, Biocompatible; D010880:Piperidines; D052999:Quinazolinones; D012828:Silicones; C010176:halofuginone