CXCR4 Antagonism to Treat Delayed Fracture Healing

A significant number of fractures develop non-union. Stem cell homing is regulated through SDF-1 and its receptor CXCR4. Stem/progenitor cell populations can be endogenously mobilised by administering growth factors with a pharmacological antagonist of CXCR4, AMD3100, which may be a means to improve fracture healing. Methods: A 1.5mm femoral osteotomy in Wistar rats was stabilised with an external fixator. Rats were pre-treated with PBS(P), VEGF(V), IGF-1(I) or GCSF(G) prior to AMD3100. A control group (C) did not receive growth factors or AMD3100. Bone formation after five weeks was analysed. Results: Group P had a significant increase in total bone volume (p=0.01) and group I in % bone in the fracture gap (p=0.035). Group G showed a decrease in bone volume. All treated groups had an increase in trabecular thickness. Histology showed decreased cartilage tissue associated with increased bone in groups with improved healing, and increased fibrous tissue in poorly performing groups. Conclusion: Antagonism o...