Enhanced osteogenic promotion around dental implants with synthetic binding motif mimicking bone morphogenetic protein (BMP)‐2

Abstract

Synthetic receptor binding motif mimicking bone morphogenetic protein-2 (BMP-2) was covalently linked to titanium (Ti) surfaces through a chemical conjugation process. The composition and properties of surface-modified Ti were investigated by XPS as well as by measuring surface radioactivity. In vitro tests were conducted with osteoblast-like MC3T3-E1 cells to assess cell attachment, morphology, and expression of osteogenic marker in the cells grown on modified Ti surfaces. In addition, in vivo experiments involved implants in mandibular bone defects of beagles to evaluate the effect of surface modification on bone regeneration. Results of XPS measurements showed a complete and homogeneous peptide overlayer on the Ti surfaces; the content was further measured by gamma counting. Biological evaluations showed that the biochemically modified Ti samples were active in terms of cell attachment behavior. The MC3T3-E1 cell growth rate, marker protein expression, and alkaline phosphatase production of the peptide-modified surfaces were all higher than those of control Ti. Importantly, the implants in the canine mandibles showed significant increase of bone growth when modified with bioactive peptide, thereby confirming that biochemical modifications of Ti surfaces can enhance the rate of bone healing as compared with untreated Ti surfaces.

Direct laser writing-mediated generation of standardized topographies for dental implant surface optimization

“…The modification of titanium surfaces represents a frequently used approach for the optimization of implant biocompatibility. In the majority of cases, variations are of biochemical and/or physicochemical nature and include the binding of bioactive signal molecules 5 as well as modulations of surface hydrophilicity 3 or structure. 10 In most approaches, structural modifications are generated by physical or chemical impacts (e.g., sandblasting or etching), the results of which can be adjusted by altering process parameters, but, however, may be regarded as unorganized or not completely controllable in detail.…”

“…2 In the past, attempts for an optimization of the dental implant surface mainly focused on the interaction between titanium (as the material of choice for most constructs) and bone tissue. Modification of the titanium surface, e.g., by altering its hydrophilicity, 3 by providing integrin binding ligands or growth factor motifs, 4,5 by structural modifications, 6,7 or combinations of the latter 8,9 have been analyzed for an enhancement of cell growth, adhesion, and/or differentiation of osteoblasts, osteoblastlike cells, or mesenchymal stem cells. While such functionalizations frequently induced alterations in one of the parameters mentioned above, many of them have not been evaluated for an optimization of the balance between proliferation and differentiation, which is required for optimized osseointegration.…”

How to use BMP-2 for clinical applications? A review on pros and cons of existing delivery strategies

“…BMP-2 peptides covalently bound to glass, titanium, cobalt chromium (CoCr) and gold substrate have been shown to enhance and accelerate the growth and differentiation of osteoblasts and other cell lines. Chemical immobilization of synthetic peptides onto titanium implants was conducted to evaluate the in vitro and in vivo osteointegration capacity [119]. A peptide mimicking both, the wrist and the knuckle epitope was chemically synthesized using a so-called F-moc chemistry with an additional N-terminal modification by a cysteine-containing spacer which eases chemical conjugation onto implant surfaces.…”

Biofunctionalization of Metals with Polymers

“…Ectopic bone formation by BMP-2 in animals has been well established following the first reports of BMP-2 by the Urist research group [40][41][42]. Synthetic receptor binding motif mimicking BMP-2 is covalently linked to Ti surfaces through a chemical conjunction process [43]. A complete and homogeneous peptide overlayer on the Ti surfaces; the content is further measured by gamma counting.…”