Mesenchymal stem cells (MSCs), found within bone marrow and periosteum have long been studied for their regenerative potential in clinical medicine and surgery. At the time of writing, MSCs are routinely clinically implanted into a range of clinical sites ranging from orthopaedic fractures to arthritic joints. The research presented in this thesis relates to their use in the enhancement of orthopaedic fracture repair. Specifically, identifying and developing mechanisms to promote the enhancement of MSC osteogenic potential raising the possibility of addition to a fracture site and assistance with the healing process.
The effect of exposure of MSCs to a pneumatic shockwave in the context of osteogenic upregulation was studied. Prior work demonstrated increased osteogenic upregulation in MSCs exposed to a pneumatic shockwave with a view to identify novel pharmacological protective agents to combat blast induced heterotopic ossification. These prior experiments demonstrated that both adherent and suspended MSCs may be enhanced by exposure to a shockwave stimulus in terms of osteogenic upregulation. This relationship was further explored here in a translational scenario. A novel, small-scale shock tube capable of use in cellular biological research was developed and characterised. Osteogenic upregulation of MSCs in suspension was demonstrated in comparison to un-exposed controls. In addition, a demonstrated paucity of MSCs in clinically obtained bone marrow aspirate concentrate detracts from hypothetical clinical utility. For this reason, focus was placed on a colonially expanded MSC population.
Prior work has previously demonstrated an increase in osteogenesis in response to elevated temperature in cultured MSC’s. As a result, apparatus to expose MSCs in suspension to temperatures that exceed their normal physiological conditions was additionally designed and characterised in addition to cellular experimentation. Initial cellular experiments suggested osteogenic upregulation was induced on exposure. Further apparatus with improved accuracy remains ready for cellular work in collaboration with an external party.
MSC exposure to shear stresses that exceed their normal physiological conditions has previously demonstrated osteogenic upregulation. Apparatus was designed and characterised to achieve this exposure whilst a cellular experimental protocol was devised and discussed. Initial experiments were carried out as a proof of concept alongside discussion of translational potential.
In finality, innovative translational designs for MSC loading modalities are suggested with a regard to existing prior art and clinical integration. Although further cellular experimentation is required to validate this approach, the translational groundwork and commercialisation direction has been clearly proposed.