Bone intramedullary reaming grafts the fracture site with CD146+ skeletal progenitors and downmodulates the inflammatory environment

      Abstract

      Introduction

      Femoral shaft fractures generally occur in young adults following a high-energy trauma and are prone to delayed union/non-union. Novel therapies to stimulate bone regeneration will have to mimic some of the aspects of the biology of fracture healing; however, which are these aspects is unclear. Locked intramedullary nailing is the current treatment of choice for the stabilisation of femur shaft fractures, and it is associated with accelerated healing and increased union rates. These benefits were partially attributed to the reaming procedure, which, regardless of significantly destroying the haematoma, stimulates the healing response. To better understand how reaming influences healing, we evaluated the viability of the nucleated cell fraction and the frequency of CD146+ skeletal progenitors, which contain multipotent cells, in the post-reaming haematoma. We also screened the concentrations of inflammatory mediators and growth factors in the fracture site after reaming compared with those in the original haematoma.

      Methods

      Pre- and post-reaming haematomas were percutaneously aspirated from the fracture site of 15 patients with closed femoral shaft fractures. Cellular viability and the percentage of CD146+ progenitors were analysed by flow cytometry. The concentrations of cytokines and growth factors were determined by ELISA.

      Results

      AnnexinV/Pi analysis showed that the viability of the total nucleated cell fraction was decreased in the post-reaming haematoma. However, the procedure increased the percentage of CD146+ skeletal progenitors in the fracture site. Analysis of cytokines and growth factors in supernatants showed a decreased concentration of the inflammatory mediators IL-6, CCL-4, and MCP-1, along with an increase of anti-inflammatory IL-10, and the growth factors bFGF and PDGF-AB.

      Conclusion

      These findings support the view that the positive effects of reaming on fracture healing might result from mechanically grafting the fracture site with a population of skeletal progenitors that contain multipotent cells; transitioning the signalling environment to a less inflammatory state, and enhancing the availability of specific osteogenic and angiogenic factors. A better understanding of the requisite stimuli for optimal bone repair, considering the disturbances made by orthopaedic treatments, will be determinant for the development of innovative treatments for bone repair.

      Keywords

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