Fracture non-union is the failure of a fracture to heal and can confer long-term problems to the affected individual. The blast and ballistic mechanisms that typically cause combat injuries mean that fracture non-union is a particular problem amongst military personnel. Furthermore, a systematic review undertaken as part of this project showed that rates of fracture non-union have not improved over a century of warfare, highlighting the enduring clinical burden that this condition confers to defence.
With limited treatment option for fracture non-union, mesenchymal stem cells (MSCs) represent a promising therapeutic option. Bone marrow aspirate concentrate (BMAC), purported to contain high levels of MSCs, is already used in clinical practice to treat fracture non-union. Mechanotransduction describes the process through which a mechanical force can confer a biochemical signal within a cell, altering gene expression and stimulating cell differentiation. Blast victims present with a high incidence of heterotopic ossification, with the mechanism of action postulated as being a mechanotransducive transfer of energy from the blast wave stimulating osteoblastic transformation of MSCs.
The experimental aspect of this project therefore sought to investigate whether a blast wave can induce osteoblastic transformation in MSCs, potentially offering a novel therapy to aid fracture healing. Upregulation in osteogenic gene expression and calcium mineralisation was observed in MSCs following blast wave exposure. However, these findings were not reproduced in BMAC samples with flow cytometry demonstrating a marked paucity of MSCs. Subsequent work demonstrated that growth factors likely mediate the osteogenic effect of BMAC and can be enhanced following exposure of BMAC to a single blast wave.
The data presented in this thesis has shown that blast waves when used in conjunction with BMAC may provide a novel therapy for the treatment of fractures at high risk of developing a non-union, such as those sustained in combat from a blast mechanism. Development of subsequent pre-clinical and clinical studies is required to translate this work into a feasible clinical option to aid in the treatment and avoidance of fracture non-union.