Abstract

Introduction: Healing of bone defects represents clinical challenge due to limited effectiveness of available treatments. Enhancement of endogenous mesenchymal stem cells (MSCs) mobilization and homing is a promising approach for bone regeneration. The present study tested the hypothesis that stem cell mobilization and homing by systemic Substance P (SP) and local Stromal Cell-Derived Factor-1 (SDF-1α) treatment can augment low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) induced ectopic bone formation in a rat model.

Materials and Methods: Rats received intravenous injections of either saline or SP in implantation day as well as postoperative day 1 of the subcutaneous implantation of absorbable collagen sponges (ACS's) loaded with saline or suboptimal dose of rhBMP-2 alone or suboptimal dose of rhBMP-2 and SDF-1α. At 28th days, bone formation in the explanted scaffolds was examined for alkaline phosphatase activity (ALP), osteopontin (OPN) assays as well as radiologically and histologically.

Results: systemic SP and local SDF-1 α significantly enhanced ALP activity in the explanted bony nodules of the studied groups as compared to controls. Radiological and histological assessment were consistant with biochemical results showing much more mature bone formation.

Conclusion: The study provides evidence of the effective treatment of systemic SP and local SDF-1 α in enhancement of in vivo trafficking of MSC's in low-dose rhBMP induced ectopic bone formation.