Repair of Bone Fracture Non-Union with BMP-2 Growth Factor on Hydroxyapatite Scaffolds
Amy Zhou
Introduction Fracture non-union (failure to heal) is a major clinical problem exhibiting a prevalence of 5-10% in bone fracture patients.(1) Currently, there are four options of bone fracture repair: autografts, allografts, xenografts, and synthetic bone scaffolds.(2) Synthetic bone scaffolds provide unique opportunities to simultaneously reduce graft rejection, prevent infection transmission, and improve availability of bone-grafts.(3) Methods Synthetic bone scaffolds are 3-dimension structures generated from materials, like collagen and hydroxyapatite. Bone morphogenic protein (BMP-2) is the most potent growth factor loaded onto scaffolds. (4) BMP-2 induced osteoblast differentiation promotes bone regrowth. C2C12 cell cultures and mouse models were used to illustrate its mechanisms.(4) BMP-2 was freeze dried onto hydroxyapatite collagen scaffolds and applied to rat bone marrow derived mesenchymal stem cells (BMSCs) to study the biocompatibility of BMP-2 loaded scaffolds.(5) Scanning electron microscopy (SEM) qualitatively confirmed distribution of BMSCs on scaffold surfaces.(5) Alkaline phosphatase (ALP) quantified osteoblast differentiation and indicated BMP-2 activity. (5) Release kinetics of BMP-2 were evaluated by fluorescence-based retention and ELISA assays. (6) Results Researchers used C2C12 cell cultures and mouse models to find that BMP-2 specifically stimulated osteoblast differentiation through two pathways: Smad 5 and calcineurin.(4) The essentiality of BMP-2 induction for osteoblast differentiation led researchers to further study the biocompatibility and pharmacokinetics of BMP-2 to determine its suitability for clinical applications.(4) BMP-2 was added to BMSCs plated with hydroxyapatite collagen scaffold, and found to increase cell adhesion rate compared to control groups.(5) SEM visualization confirmed biocompatibility of BMP-2 on BMSCs adherence to scaffold surfaces.(5) Later, pharmacokinetic studies of prepared BMP-2 loaded hydroxyapatite scaffolds were measured for BMP-2 release over the course of 14 weeks using ELISA and fluorescence-based retention assay.(6) Both assays confirmed initial burst release followed by sustained release of BMP-2 over 14 weeks. This was a desired release rate to prevent adverse effects of BMP-2, including ectopic bone formation. (6) ALP activity confirmed release of biologically active BMP-2 over 14 weeks. (6) Conclusion With its biocompatibility and effective pharmacokinetics, BMP-2 has been FDA approved as a treatment option for small-sized procedures. (7) However, BMP-2 loaded synthetic scaffolds have not been successfully applied to fracture non-union, so further research is needed to optimize its clinical applications.
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