Abstract
Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and platelets, has recently attracted the attention of clinicians as a new optional means for bone engineering. We previously reported that the osteoinductive effect of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co-transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This study aims to investigate whether BMC can effectively promote bone formation induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP-2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an automated blood separator. The BMC was then seeded onto β-TCP granules pre-adsorbed with a suboptimal-dose (minimum concentration to induce bone formation at 2 weeks in mice) of recombinant human (rh) BMP-2. These specimens were transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the induction of ectopic bone formation was assessed 2 and 4 weeks post-transplantation. Transplantations of five other groups [PB, PRP, platelet-poor plasma (PPP), bone marrow aspirate (BM), and BM-PPP] were employed as experimental controls. Then, to clarify the effects on vertical bone augmentation, specimens from the six groups were transplanted for on-lay placement on the craniums of mice. The results indicated that BMC, which contained an approximately 2.5-fold increase in the number of MNCs compared to PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation. On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites far from the calvarial bone. In conclusion, the addition of BMC could reduce the amount of rhBMP-2 by one-half via its synergistic effect on early-phase osteoinduction. We propose here that BMC transplantation facilitates the clinical use of rhBMP-2 as an alternative strategy for bone engineering.
Highlights
Current surgical strategies for healing bone defects arising from trauma or disease employ either autogenous bone grafts or alloplastic bone substitutes [1]
The study outcomes were: 1) bone marrow concentrate (BMC) accelerated bone formation from the early-phase of transplantation when co-delivered with a suboptimal-dose of rhBMP-2, 2) BMC rather than platelet-rich plasma (PRP) enabled a reduction in the dose of rhBMP-2 by its synergistic action in vivo
This result strongly suggested that growth factors released from platelets in the PRP function to promote bone formation in the presence of rhBMP-2, as evidenced by the low numbers of platelets in bone marrow aspirate (BM) compared to PRP
Summary
Current surgical strategies for healing bone defects arising from trauma or disease employ either autogenous bone grafts or alloplastic bone substitutes [1]. Tissue engineering has recently been considered a potential alternative strategy to bone reconstruction, since it is thought to be less invasive and safer than conventional methods [5,6]. For this reason, growth factors and stem cells are receiving significant attention as key elements in tissue engineering that can confer osteoinducibility to alloplastic bone substitutes. To expand the clinical utility of rhBMP2, recent studies have focused on reducing the dose of rhBMP-2 without attenuating its osteoinductive function by combining rhBMP-2 with other growth factors, stem cells, or sustained-release materials [13,14]. An efficient delivery method that avoids the undesirable side effects of rhBMP-2 remains to be established
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