The use of synthetic clay to enhance fracture healing and bone regeneration

Abstract

Fractures are extremely common and can take months to heal. Bone graft material is used to stimulate healing and fill voids in reconstructive surgery. Bone Morphogenetic Protein (BMP) has been used clinically to stimulate fracture healing and arthrodesis; however inefficient delivery methods necessitated the use of high doses which resulted in significant side effects. Materials currently used for bone grafting such as: autograft, allograft and synthetic bone products all have significant limitations. These studies have investigated the ability of Laponite, a synthetic clay, to facilitate growth factor delivery to enhance fracture healing and improve the osteogenicity of graft material produced using additive manufacture. Initial studies culturing cells with Laponite demonstrated the biocompatibility of this material. Subsequently, the ability of Laponite to deliver and localise active growth factor was shown using Human Umbilical Vein Endothelial Cells and Myoblast cell cultures. Feasibility of combining Laponite with Additive Manufacturing techniques to produce bone graft material was assessed in vitro. In murine studies Laponite was observed to enhance the osteogenic effect of BMP applied to allograft and, furthermore, reduce the dose of BMP required to mediate ectopic bone formation within collagen sponge. Finally, in an ovine femoral defect Laponite was observed to convey active BMP. The in vitro and in vivo evidence for the ability of Laponite to deliver BMP presented in this thesis demonstrates the exciting potential of Laponite to accelerate fracture healing and enhance the osteogenicity of graft material.

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ORCID for Richard Oreffo: orcid.org/0000-0001-5995-6726

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