In vivo study of the effect of RGD treatment on bone ongrowth on press-fit titanium alloy implants

Elmengaard, Brian; Bechtold, Joan E.; Søballe, Kjeld

doi:10.1016/j.biomaterials.2004.09.039

Cited by 176 publications

(127 citation statements)

References 21 publications

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“…35 While various bioactive peptides (RGD, COL1, fibronectin) have shown initial increases in cellular adhesion of cells attached to the modified Ti surface their effect on late differentiation has had mixed success. 22,[36][37][38][39][40][41][42][43] Our study shows that presence of P15 increases osteogenic gene expression and stimulates osteoblastic activity; as shown by qPCR and histochemical staining of cells grown on Ti-P15 surface compared to control.…”

Section: Discussionsupporting

confidence: 51%

Covalent attachment of P15 peptide to titanium surfaces enhances cell attachment, spreading, and osteogenic gene expression

Liu

Limthongkul

Sidhu

et al. 2012

Journal Orthopaedic Research

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P15, a synthetic 15 amino acid peptide, mimics the cell-binding domain within the alpha-1 chain of human collagen is being tested in clinical trials to determine if it enhances bone formation in spinal fusions. We hypothesize that covalent attachment of P15 to titanium implants may also serve to promote osseointegration. To test this hypothesis, we measured osteoblast and mesenchymal cell adhesion, proliferation, and maturation on P15 tethered to a titanium (Ti-P15) surface. P15 peptide was covalently bonded to titanium alloy surfaces and incubated with osteoblast like cells. Cell toxicity, adhesion, spreading, and differentiation was then evaluated. Real-time quantitative PCR, Western blot analysis, and fluorescent immunohistochemistry was performed to measure osteoblast gene expression and differentiation. There was no evidence of toxicity. Significant increases in early cell attachment, spreading, and proliferation were observed on the Ti-P15 surface. Increased filapodial attachments, a 2 integrin expression, and phosphorylated focal adhesion kinase immunostaining indicated activation of integrin signaling pathways. qRT-PCR analysis indicated there was significant increase in osteogenic differentiation markers in cells grown on Ti-P15 compared to control-Ti. Western blotting confirmed these findings. Surface modification of titanium with P15 significantly increased cell attachment, spreading, osteogenic gene expression, and differentiation. Results of this study suggest that Ti-P15 has the potential to safely enhance bone formation and promote osseointegration of titanium implants. ß

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Section: Discussionsupporting

confidence: 51%

Covalent attachment of P15 peptide to titanium surfaces enhances cell attachment, spreading, and osteogenic gene expression

Liu

Limthongkul

Sidhu

et al. 2012

Journal Orthopaedic Research

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show abstract

“…via functional groups like hydroxyl-, amino-, or carboxyl groups. RGD-functionalized materials are reported to improve early bone ingrowth and matrix mineralization in implanted constructs (113,121) and to induce more bone contact to the implant (114,122). Fig.…”

Section: Ecm Proteins and Peptide Sequence Immobilizationmentioning

confidence: 99%

Organic–Inorganic Surface Modifications for Titanium Implant Surfaces

et al. 2008

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Abstract. This paper reviews current physicochemical and biochemical coating techniques that are investigated to enhance bone regeneration at the interface of titanium implant materials. By applying coatings onto titanium surfaces that mimic the organic and inorganic components of living bone tissue, a physiological transition between the non-physiological titanium surface and surrounding bone tissue can be established. In this way, the coated titanium implants stimulate bone formation from the implant surface, thereby enhancing early and strong fixation of bone-substituting implants. As such, a continuous transition from bone tissue to implant surface is induced. This review presents an overview of various techniques that can be used to this end, and that are inspired by either inorganic (calcium phosphate) or organic (extracellular matrix components, growth factors, enzymes, etc.) components of natural bone tissue. The combination, however, of both organic and inorganic constituents is expected to result into truly bone-resembling coatings, and as such to a new generation of surface-modified titanium implants with improved functionality and biological efficacy.

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“…The most common approach relies on the presentation of the arginine-glycine-aspartic acid (RGD) adhesive sequence derived from FN. While synthetic and natural materials functionalized with RGD oligopeptides support integrin-mediated adhesion, proliferation, and differentiation in vitro, mounting evidence indicates that this biomaterial surface engineering strategy does not enhance biomedical implant integration or function in rigorous animal models [14][15][16]. Based on previous in vitro work demonstrating that integrin binding specificity (α 5 β 1 vs. α V β 3 ) regulates osteoblastic differentiation [17], we hypothesized that the marginal healing responses to RGDfunctionalized implants arise from the lack of selectivity of this ligand for specific integrins.…”

Section: Introductionmentioning

confidence: 99%

The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration

et al. 2008

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Implant osseointegration, defined as bone apposition and functional fixation, is a requisite for clinical success in orthopaedic and dental applications, many of which are restricted by implant loosening. Modification of implants to present bioactive motifs such as the RGD cell-adhesive sequence from fibronectin (FN) represents a promising approach in regenerative medicine. However, these biomimetic strategies have yielded only marginal enhancements in tissue healing in vivo. In this study, clinical-grade titanium implants were grafted with a non-fouling oligo(ethylene glycol)-substituted polymer coating functionalized with controlled densities of ligands of varying specificity for target integrin receptors. Biomaterials presenting the α 5 β 1 -integrin-specific FN fragment FNIII 7-10 enhanced osteoblastic differentiation in bone marrow stromal cells compared to unmodified titanium and RGD-presenting surfaces. Importantly, FNIII 7-10 -functionalized titanium significantly improved functional implant osseointegration compared to RGD-functionalized and unmodified titanium in vivo. This study demonstrates that bioactive coatings that promote integrin binding specificity regulate marrow-derived progenitor osteoblastic differentiation and enhance healing responses and functional integration of biomedical implants. This work identifies an innovative strategy for the rational design of biomaterials for regenerative medicine.

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In vivo study of the effect of RGD treatment on bone ongrowth on press-fit titanium alloy implants

Cited by 176 publications

References 21 publications

Covalent attachment of P15 peptide to titanium surfaces enhances cell attachment, spreading, and osteogenic gene expression

Covalent attachment of P15 peptide to titanium surfaces enhances cell attachment, spreading, and osteogenic gene expression

Organic–Inorganic Surface Modifications for Titanium Implant Surfaces

The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration

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