Covalently grafted BMP-7 peptide to reduce macrophage/monocyte activity: an in vitro study on cobalt chromium alloy.
Cobalt chromium (CoCr) alloy is widely used in orthopedic implants but its functional longevity is susceptible to inflammation related complications. Reduction of the development of chronic inflammation on the biomaterial surface would enhance direct bone-implant bonding and improve implant survival and long-term results. The BMP-7 peptide was derived from the knuckle epitope of bone morphogenic protein-7 (BMP-7) and was conjugated via a cysteine amino acid at the N-terminus. Mouse RAW 264.7 monocytes/macrophages were seeded on the CoCr substrates and inflammation was induced via lipopolysaccharide (LPS) challenge. The effects of BMP-7 peptide on inflammation were evaluated by measuring the expression of inflammatory markers like toll-like receptor-4 (TLR-4), tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1). ELISA and qPCR assays were used to study the inflammatory signals. BMP-7 signaling pathway activation was shown by the presence of phosphorylation of Smad1/5/8. Utilizing the reactivity of polydopamine films to immobilize BMP-7 peptide onto metal substrates may provide a promising approach for applications in situations where reduction of inflammation around implants would be beneficial in improving surgical outcome, bone healing, and implant integration.
Orthopaedic Diagnostic Centre, National University Hospital, Singapore.
Hark Chuan
HC
Tan
Chye Khoon
CK
Poh
Yanli
Y
Cai
Min Thun
MT
Soe
Wilson
W
Wang
D000497:Alloys / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D002857:Chromium / Q000737:chemistry / Q000633:toxicity*; D003035:Cobalt / Q000737:chemistry / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D007155:Immunologic Factors / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000497:Alloys; D055419:Bone Morphogenetic Protein 7; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007155:Immunologic Factors; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002857:Chromium; D003035:Cobalt