Bone regeneration remains one of the major clinical needs in orthopedics, and advanced and alternative strategies involving bone substitutes, cells, and growth factors (GFs) are mandatory. The purpose of this study was to evaluate whether the association of autologous bone marrow mesenchymal stem cells (BMSC), isolated by ‘one-step surgical procedure’, and activated platelet rich plasma (PRP) improves osseointegration and bone formation of a hydroxyapatite-coated titanium (Ti-HA) implant, already in clinical use, in a rabbit cancellous defect. The GFs present in plasma, in inactivated and activated PRP were also tested. At 2 weeks, histology and histomorphometry highlighted increased bone-to-implant contact (BIC) in Ti-HA combined with BMSC and PRP in comparison to Ti-HA alone and Ti-HA + PRP. The combined effect of BMSC and PRP peaked at 4 weeks where the BIC value was higher than all other treatments. At both experimental times, newly formed bone (Trabecular Bone Volume, BV/TV) in all tested treatments showed increased values in comparison to Ti-HA alone. At 4 weeks Ti-HA + PRP + BMSC showed the highest BV/TV and the highest osteoblasts number; additionally, a higher osteoid surface and bone formation rate were found in Ti-HA + BMSC + PRP than in all other treatments. Finally, the analyses of GFs revealed higher values in the activated PRP in comparison to plasma and to non-activated PRP. The study suggests that the combination of autologous activated PRP, as a carrier for BMSCs, is a promising regenerative strategy for bone formation, osseointegration, and mineralization of bone implants.
RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation