Stromal cell-derived factor-1 stimulates cell recruitment, vascularization and osteogenic differentiation.

The use of growth factors in osteogenic constructs to promote recruitment of bone forming endogenous cells is not clear, while the advantage of circumventing cell seeding techniques before implantation is highly recognized. Therefore, the additive effect of the chemokine stromal cell-derived factor-1α (SDF-1α) on endogenous cell recruitment and vascularization was investigated in a hybrid construct, consisting of a ceramic biomaterial, hydrogel, and SDF-1α, in an ectopic mouse model. We demonstrated in vivo that local presence of low concentrations of SDF-1α resulted in a significant increase in recruited endogenous cells, which remained present for several weeks. SDF-1α stimulated vascularization in these hybrid constructs, as shown by the enhanced formation of erythrocyte-filled vessels. The presence of CD31-positive capillaries/small vessels after 6 weeks in vivo substantiated this finding. The SDF-1α treatment showed increased number of cells that could differentiate to the osteogenic lineage after 6 weeks of implantation, demonstrated by expression of collagen I and osteocalcin. Altogether, we show here the beneficial effects of the local application of a single growth factor in a hybrid construct on angiogenesis and osteogenic differentiation, which might contribute to the development of cell-free bone substitutes.