title: Anti-fibrosis effect of BMP-7 peptide functionalization on cobalt chromium alloy.
abstract: Orthopedic metallic prosthetic implants are commonly made of cobalt chromium (CoCr) alloys. However, such metal-based implants are susceptible to fibrous capsule formation on the implant surface after implantation. At the bone-implant interface, this capsule can prevent implant integration, resulting in loosening and failure. Minimizing the development of such a capsule on the CoCr surface would improve direct bone-implant bonding leading to long-term implant functionality. We evaluated the anti-fibrosis effect of bone morphogenic protein-7 (BMP-7) peptide covalently bonded to CoCr alloy. This peptide, a biomimetic derivation of the knuckle epitope of BMP-7, was conjugated at the N-terminus with a cysteine amino acid. X-ray photoelectron spectroscopy (XPS) and probe binding assay were used to evaluate different stages of grafting and surface functionalization using polydopamine coating. Cellular functions were studied using fibroblast attachment, cell proliferation, and MTT assays. Fibroblasts were grown on functionalized and pristine CoCr substrates, and the efficacy of BMP-7 peptide on anti-fibrosis was analyzed via gene expression and protein expression of fibrosis markers ACTA2, Collagen 1A1, and fibronectin. The peptide functionalized substrates showed significant reduction of fibrosis markers expression after 1 week of incubation compared to controls. BMP-7 signaling pathway activation was shown by the presence of phosphorylation of Smad1/5/8. These findings may contribute to the improvement of CoCr implants in orthopedic surgery applications.
authors: Department of Orthopaedic Surgery, National University of Singapore, Kent Ridge, Singapore 119074, Singapore.
authors: Hark Chuan
authors: HC
authors: Tan
authors: Chye Khoon
authors: CK
authors: Poh
authors: Yanli
authors: Y
authors: Cai
authors: Wilson
authors: W
authors: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000737:chemistry / Q000502:physiology*; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002858:Chromium Alloys / Q000737:chemistry*; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D005347:Fibroblasts / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000503:physiopathology*; D051379:Mice; D041681:NIH 3T3 Cells; D060888:Real-Time Polymerase Chain Reaction; D013499:Surface Properties
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D015415:Biomarkers; D055419:Bone Morphogenetic Protein 7; D002858:Chromium Alloys; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D005353:Fibronectins