title: An in vitro assessment of titanium functionalized with polysaccharides conjugated with vascular endothelial growth factor for enhanced osseointegration and inhibition of bacterial adhesion.
abstract: The long-term success of orthopedic implants may be compromised by defective osseointegration and bacterial infection. An effective approach to minimize implant failure would be to modify the surface of the implant to make it habitable for bone-forming cells and anti-infective at the same time. In this in vitro study, the surfaces of titanium (Ti) substrates were functionalized by first covalently grafting either dopamine followed by carboxymethyl chitosan (CMCS) or hyaluronic acid-catechol (HAC). Vascular endothelial growth factor (VEGF) was then conjugated to the polysaccharide-grafted surface. Antibacterial assay with Staphylococcus aureus (S. aureus) showed that the polysaccharide-modified substrates significantly decrease bacterial adhesion. The CMCS-functionalized Ti demonstrated better antibacterial property than the HAC-functionalized Ti since CMCS is bactericidal while HA only inhibits the adhesion of bacteria without killing them. Osteoblast attachment, as well as alkaline phosphatase (ALP) activity and calcium deposition were enhanced by the immobilized VEGF on the polysaccharide-grafted Ti. Thus, Ti substrates modified with polysaccharides conjugated with VEGF can promote osteoblast functions and concurrently reduce bacterial adhesion. Since VEGF is also known to enhance angiogenesis, the VEGF-polysaccharide functionalized substrates will have promising applications in the orthopedic field.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 119260, Singapore.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Hu
authors.forename: Koon-Gee
authors.initials: KG
authors.lastname: Neoh
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Shi
authors.forename: En-Tang
authors.initials: ET
authors.lastname: Kang
authors.forename: Chyekhoon
authors.initials: C
authors.lastname: Poh
authors.forename: Wilson
authors.initials: W
authors.lastname: Wang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D004602:Elements; D055767:Immobilized Proteins / Q000378:metabolism; D008422:Materials Testing / Q000379:methods*; D051379:Mice; D008856:Microscopy, Fluorescence; D016348:Osseointegration / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D056951:Photoelectron Spectroscopy; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D055550:Protein Stability / Q000187:drug effects; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects; D013499:Surface Properties / Q000187:drug effects; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004602:Elements; D055767:Immobilized Proteins; D011134:Polysaccharides; D042461:Vascular Endothelial Growth Factor A; D014025:Titanium; D000469:Alkaline Phosphatase; D002118:Calcium