Osteoinductivity of nanostructured hydroxyapatite-functionalized gelatin modulated by human and endogenous mesenchymal stromal cells

The demand of new strategies for the induction of bone regeneration is continuously increasing. Biomimetic porous gelatin-nanocrystalline hydroxyapatite scaffolds with tailored properties were previously developed, showing a positive response in terms of cell adhesion, proliferation, and differentiation. In the present paper, we focused on their osteoinductive properties. The effect of scaffolds on osteogenic differentiation of human mesenchymal stromal cells (hMSCs) was investigated in vitro. hMSCs were seeded on GEL (type A gelatin) and GEL containing 10 wt% hydroxyapatite (GEL-HA) and cultured in osteogenic medium. Results showed that GEL and GEL-HA10 sustained hMSC differentiation, with an increased ALP activity and a higher expression of bone specific genes. The osteoinductive ability of these scaffolds was then studied in vivo in a heterotopic bone formation model in nude mice. The influence of hMSCs within the implants was examined as well. Both GEL and GEL-HA10 scaffolds mineralized when implanted without hMSCs. On the contrary, the presence of hMSC abolished or reduced mineralization of GEL and GEL-HA10 scaffolds. However, we could observe a species-specific response to the presence of HA, which stimulated osteogenic differentiation of human cells only. In conclusion, the scaffolds showed promising osteoinductive properties and may be suitable for use in confined critical defects.