Surface functionalization of titanium with carboxymethyl chitosan and immobilized bone morphogenetic protein-2 for enhanced osseointegration.

Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore.
Biomacromolecules (Impact Factor: 5.37). 05/2009; 10(6):1603-11. DOI: 10.1021/bm900203w
Source: PubMed

ABSTRACT Orthopedic implant failure has been attributed mainly to loosening of the implant from host bone, which may be due to poor bonding of the implant material to bone tissue, as well as to bacterial infection. One promising strategy to enhance tissue integration is to develop a selective biointeractive surface that simultaneously enhances bone cell function while decreasing bacterial adhesion. In this in vitro study, the surfaces of titanium alloy substrates were functionalized by first covalently grafting carboxymethyl chitosan (CMCS), followed by the conjugation of bone morphogenetic protein-2 (BMP-2) to the CMCS-grafted surface. Bacterial adhesion on the substrates was assayed with Staphylococcus aureus and Staphylococcus epidermidis . Cell functions were investigated using osteoblasts and human bone marrow-derived mesenchymal stem cells. The results showed that bacterial adhesion on both the CMCS and CMCS-BMP-2 functionalized surfaces was significantly reduced compared to that on the pristine substrates. In addition, the CMCS-BMP-2 modified substrates significantly promoted attachment, alkaline phosphatase activity, and calcium mineral deposition of both osteoblast and human bone marrow-derived mesenchymal stem cells. The achievement of the dual functions of bacterial adhesion reduction and cell function promotion by the CMCS-BMP-2 modified titanium substrates illustrates the good potential of such surfaces for enhancement of tissue integration and implant longevity.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to develop bone morphogenic protein-2 (BMP-2) immobilized PCL fibers to induce osteogenic differentiation of periodontal ligament cells (PDLCs). The PCL fiber surface was modified with heparin-dopamine (Hep-DOPA) (Hep-PCL) and further immobilized with BMP-2 (BMP-2/Hep-PCL). PCL fibers and surface-modified PCL fibers (Hep-PCL and BMP-2/Hep-PCL) were characterized by X-ray photoelectron spectroscopy (XPS) and contact angle. Osteogenic differentiation of PDLCs was demonstrated by alkaline phosphatase (ALP) activity, calcium deposition, and gene expression. The results of XPS and contact angle revealed that Hep-DOPA and BMP-2 were successfully immobilized onto the PCL surface and that the BMP-2/Hep-PCL fibers have more hydrophilic surface properties than PCL fibers alone. ALP activity, calcium deposition, and gene expression on BMP-2/Hep-PCL fibers showed significantly induced osteogenic differentiation relative to PCL fibers. Therefore, we suggest that BMP-2/Hep-PCL fibers have the potential to effectively induce osteogenic differentiation of PDLCs.
    Carbohydrate polymers. 01/2014; 99:700-9.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Orthopedic implants failures are generally related to poor osseointegration and/or bacterial infection in clinical application. Surface functionalization of an implant is one promising alternative for enhancing osseointegration and/or reducing bacterial infection, thus ensuring the long term survival of the implant. In this study, titanium (Ti) substrates were surface functionalized with a polydopamine (PDOP) film as an intermediate layer for post-immobilization of chitosan-lauric acid (Chi-LA) conjugate. Chi-LA conjugate was synthesized and characterized by Fourier transform infrared spectroscopy (FTIR) and hydrogen proton nuclear magnetic resonance (NMR) spectrometer, respectively. Lauric acid (LA), a natural saturated fatty acid, was used mainly due to its good antibacterial property. Scanning electron microscopy (SEM) and water contact angle measurements were employed to detect the morphology changes and surface wettability of Ti substrates. The results suggested that Chi-LA conjugate was successfully immobilized onto the surfaces of Ti substrates. In vitro tests confirmed that the cell adhesion, cell viability, intracellular alkaline phosphatase activity and mineralization capacity of osteoblasts were remarkably improved when cultured onto Chi-LA surface functionalized Ti substrates. Antibacterial assay against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) showed that the Chi-LA modified Ti substrates efficiently inhibited the adhesion and growth of bacteria. Overall, this study developed a promising approach to fabricate functional Ti-based orthopedic implants, which could enhance the biological functions of osteoblasts and concurrently reduce bacteria adhesion.
    Colloids and surfaces B: Biointerfaces 05/2014; · 3.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: By means of plasma polymerization, positively charged, nanometre-thin coatings can be applied to implant surfaces. The aim of the present study was to quantify the adhesion of human bone cells in vitro and to evaluate the bone ongrowth in vivo, on titanium surfaces modified by plasma polymer coatings. Different implant surface configurations were examined: titanium alloy (Ti6Al4V) coated with plasma-polymerized allylamine (PPAAm) and plasma-polymerized ethylenediamine (PPEDA) versus uncoated. Shear stress on human osteoblast-like MG-63 cells was investigated in vitro using a spinning disc device. Furthermore, bone-to-implant contact (BIC) was evaluated in vivo. Custom-made conical titanium implants were inserted at the medial tibia of female Sprague-Dawley rats. After a follow-up of six weeks, the BIC was determined by means of histomorphometry. The quantification of cell adhesion showed a significantly higher shear stress for MG-63 cells on PPAAm and PPEDA compared to uncoated Ti6Al4V. Uncoated titanium alloyed implants showed the lowest BIC (40.4%). Implants with PPAAm coating revealed a clear but not significant increase of the BIC (58.5%) and implants with PPEDA a significantly increased BIC (63.7%). In conclusion, plasma polymer coatings demonstrate enhanced cell adhesion and bone ongrowth compared to uncoated titanium surfaces.
    International Journal of Molecular Sciences 01/2014; 15(2):2454-64. · 2.46 Impact Factor