Abstract
BackgroundMesenchymal stem cells (MSCs) can be differentiated into an osteoblastic lineage in the presence of growth factors (GFs). Platelet-rich plasma (PRP), which can be easily isolated from whole blood, contains a large amount of GFs, and, therefore, promotes bone growth and regeneration. The main goal of this work was to develop and investigate the effect of a new sandwich-like bone scaffold which combines a nano-calcium sulfate (nCS) disc along with PRP fibrin gel (nCS/PRP) with BMP2-modified MSCs on bone repair and regeneration in rat critical-sized calvarial defects.MethodsWe evaluated the cytotoxicity, osteogenic differentiation and mineralization effect of PRP extract on BMP2-modified MSCs and constructed a sandwich-like nCS/PRP scaffold (mimicking the nano-calcium matrix of bone and carrying multi GFs in the PRP) containing BMP2-modified MSCs. The capacity of this multifunctional bone regeneration system in promoting bone repair was assessed in vivo in a rat critical-sized (8 mm) calvarial bone defect model.ResultsWe developed an optimized nCS/PRP sandwich-like scaffold. Scanning electron microscopy (SEM) results showed that nCS/PRP are polyporous with an average pore diameter of 70–80 μm and the cells can survive in the nCS/PRP scaffold. PRP extract dramatically stimulated proliferation and differentiation of BMP2-modified MSCs in vitro. Our in vivo results showed that the combination of BMP2-modified MSCs and nCS/PRP scaffold dramatically increased new bone regeneration compared with the groups without PRP and/or BMP2.ConclusionsnCS/PRP scaffolds containing BMP2-modified MSCs successfully promotes bone regeneration in critical-sized bone defects. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for critical-sized bone defects.
Highlights
Mesenchymal stem cells (MSCs) can be differentiated into an osteoblastic lineage in the presence of growth factors (GFs)
Scanning electron microscopy (SEM) analysis showed that nano-calcium sulfate (nCS) scaffolds are polyporous with an average pore diameter of 70–80 μm (Fig. 2a) and the platelets could attach on the nCS/Platelet-rich plasma (PRP) scaffolds (Fig. 2b)
Our results showed that the combination of PRP and MSCs significantly increased the osteogenic differentiation and proliferation, which can be reasonably explained since PRP consists primarily of platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) and TGF-beta, which promote osteoblast proliferation and maturation [27]
Summary
Mesenchymal stem cells (MSCs) can be differentiated into an osteoblastic lineage in the presence of growth factors (GFs). For critical-sized bone defects, conventional treatment methods use autografts, allografts, xenografts, and synthetic bone grafts These grafts have shown satisfactory results of bone regeneration, they often possess disadvantages [1] including donor site morbidity, shortage of autografts, risk of disease transmission and immune rejection [2, 3]. The advantages in the use of MSCs resides in the fact that unlike autogenous grafts, which are not available, even a small portion of MSCs derived from tissue can be expanded in in vitro culture for transplantation into defects to advance repair and remodeling of several tissues [7, 8] Since these MSCs can be autologous (obtained from the same patient), this decreases the risk of disease transmission and immune rejection
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