A Murine Model of Implant Osseointegration

Objectives: An age-related decrease in bone regenerative capacity combined with poor systemic bone quality leads to poor integration of implants into host bone in the cranio-facial, axial and appendicular skeleton. Fibroblast growth factors (FGF) are anabolic agents for skeletal cells and disruption of their signaling pathways results in a variety of skeletal defects. FGFR3-/- mice exhibit poor bone quality and defects in bone mineralization at a young age making them a suitable model to study implant osseointegration in response to interventions including surface topography and stem cell transplantation.

Methods: Smooth and micro-textured implants are fabricated using plasma vapor deposition of titanium on nylon line at the McGill Institute for Advanced Materials. Implants are introduced into the femoral canal of aged wild type (WT) and FGFR3-/- (KO) mice via the knee joint and left for 6 weeks before harvesting for micro-CT and histological analyses. Bone marrow is harvested from young adult WT donor mice for transplantation into irradiated FGFR3-/- recipient mice at the time of implantation.

Results: Quantitative micro-CT and un-decalcified histological analyses show significantly more bone apposed to micro-textured compared with smooth implant surfaces in WT and FGFR3-/- mice. The fibrous response to smooth implants is significantly greater in the KO mice. Preliminary data indicates that 15Gy is sufficient to ablate 85% of the endogenous marrow, which contains pre-osteoblasts, in recipient mice.

Conclusions: The FGFR3-/- mouse is shown to be a useful pre-clinical model to study novel therapeutic interventions to enhance bone healing around implants. The demonstrated similarities between the molecular mechanisms that regulate bone development and bone regeneration and repair in mice and humans predict rapid translation of the information from the mouse model to clinical applications.