title: Immobilization strategy for optimizing VEGF's concurrent bioactivity towards endothelial cells and osteoblasts on implant surfaces.
abstract: Orthopedic implant failure is mainly due to defective osseointegration and bacterial infection. Hence, a promising strategy to overcome these two problems is to functionalize the implant surface with both growth factors (GFs) and anti-infective agents. Covalent immobilization is widely used for such functionalization, but few studies have investigated the possible decrease in the GF's bioactivity as a result of conformational changes upon immobilization. In our study, vascular endothelial growth factor (VEGF) was immobilized on titanium surface via either covalent binding or heparin-VEGF interaction, and its bioactivity on endothelial cells (ECs) was compared. Although a similar surface density of immobilized VEGF was achieved by these two strategies, the bioactivity of the covalently immobilized VEGF on EC functions is significantly lower than that of the heparin-bound VEGF. The heparin-bound VEGF also enhanced mineralization in an osteoblast/endothelial cell co-culture to a much greater extent than in an osteoblast monoculture, illustrating the importance of crosstalk between osteoblasts and endothelial cells. In addition, the surface of the substrates with heparin-bound VEGF is highly hydrophilic and negatively-charged, which significantly inhibits Staphylococcus aureus adhesion. These results suggest that our strategy of immobilizing VEGF on titanium via heparin-VEGF interaction can preserve the GF's bioactivity on both osseous and vascular components and concomitantly reduce bacterial infection, which is promising to enhance the long-term stability of implants.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, 117576 Singapore, Singapore.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Hu
authors.forename: Koon Gee
authors.initials: KG
authors.lastname: Neoh
authors.forename: Jieyu
authors.initials: J
authors.lastname: Zhang
authors.forename: En-Tang
authors.initials: ET
authors.lastname: Kang
authors.forename: Wilson
authors.initials: W
authors.lastname: Wang
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry*; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006493:Heparin / Q000737:chemistry; D006801:Humans; D055767:Immobilized Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D016348:Osseointegration / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019736:Prostheses and Implants; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D055767:Immobilized Proteins; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D006493:Heparin; D014025:Titanium