The effect of platelet rich plasma on bone regeneration
Fernandes, Gabriela Jude
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Background: Bone regeneration is a complicated and well-orchestrated physiological process. Since Periodontitis, trauma, tumor and many other diseases can cause bone defect or loss, regeneration of the lost hard tissue is of primary importance. And although, autogenous bone grafts have been considered as the gold standard, additional surgical intervention and donor site morbidity are its limitation. Mesenchymal stem cells (MSCs) are predominantly employed in the treatment of bone defects due to its predilection towards metamorphosing into an osteogenic lineage in the presence of a catalyst. Platelet rich plasma (PRP), a whole blood derivative, is known to consist of a cocktail of growth factors like PDGF, TGF-beta and IGF that enable the regeneration of bone and that enhances the osteogenic differentiation and cellular proliferation of MSCs, whereas, Bone Morphogenic Protein-2(Bmp-2) promotes the osteogenic differentiationof the MSCs. However, the high degradation rate of fibrin leads to the dissociation of the growth factors even before the process of bone regeneration has begun. Hence, it is imperative to deliver these factors via a carrier through a controlled process in a slow manner.Alginate being biocompatible and biodegradable, was employed as a carrier for the PRP. Hence, for the first time, the combined effect of Bmp-2 and the sustained release of PRP on MSCs was studied in vitro and the sustained release of PRP on the wound healing of a fracture defect model ex vivo. Methods: After optimizing the concentration of the alginate for the microspheres, the osteogenic and mineralization effect of BMP-2 and PRP (both immediate and sustained release) as a single entity and in conjunction with each other, on MSCs was studied. Moreover, a self-setting alginate hydrogel carrying PRP was designed and tested on a femur defect model ex-vivo for 7 days in an osteogenic media. Futhermore, the effect of PRP was studied on the sutures of the embryonic (E15) mouse calvaria ex vivo. Results: Our results demonstrated a significantly higher Alkaline Phosphatase (ALP)and Calcium Mineralization activity with the use of sustained release PRP and Bmp-2. Additionally, there was an increased cellular proliferation of the MSCs with an increase in PRP concentration, whereas, 2.5%-10% of PRP displayed good ALP activity on the cells in vitro. Moreover, a self setting alginate hydrogel carrying PRP was designed and tested on a femur defect model ex vivo for 7 days in an osteogenic media. The radiographs of the bone demonstrated an excellent healing of the fracture with almost complete regeneration of the defect. Furthermore, the histological sections of the embryonic calvaria revealed that PRP leads to suture fusion. Conclusions: Together, these results demonstrate that sustained release of PRP can significantly promote the regeneration of bone when delivered as a single entity, with BMP-2 or with MSCs. The clinical implications would involve incorporating the alginate microspheres containing PRP into injectable beta-TCP or Nano calcium sulfate along with MSCs.