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Title: Dynamic loading of periosteum-derived mesenchymal stromal cells
Author: Sory, David Roger Raymond
ISNI:       0000 0004 7223 4500
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Explosive-generated waves exhibit high-energy loading profiles featured with mechanical characteristics applied over a wide range of strain rates. Recent decades have seen unprecedented occurrence of high-energy trauma associated with blast wave exposure. One such blast-specific pathology is blast-induced heterotopic ossification (bHO), which refers to ectopic bone formation due to inappropriate mesenchymal stromal cell (MSC) osteogenesis in non-skeletal tissues. Significant effort has been made into deciphering the molecular mechanisms that allow the onset of bHO, however little research has been reported on the exact role of the biomechanical processes involved in transducing blast-associated mechanical stimuli into molecular events stimulating osteogenesis in MSCs. The research presented in this thesis investigated the stimulation of osteogenesis in periosteum-derived mesenchymal stromal cells (PO MSCs) in response to mechanical insults simulating blast landmine trauma. This involved the development of experimental biocompatible in vitro platforms and the tailoring of biomechanically-relevant stimuli of varying stress intensities (up to 70 MPa), and strain rates (0.01 to 3000 /s). Subsequently, cell health and the stimulation of osteogenesis were investigated by studying the expression of Runx2 and Osteocalcin (OC) genes. We found that cell health was not affected by single-pulse loadings of wide range of impulse levels (0.20 to 95000 N.s). We showed evidence of mechanically-stimulated osteogenesis in PO MSCs through the upregulation of Runx2 and OC genes in loaded samples. Furthermore, our results highlighted that the stimulation of osteogenesis in MSCs did not result solely from the effect a single mechanical parameter, but rather the combined action of several features. We showed that osteogenesis stimulation in MSCs arised from the complex interplay between the mechanical characteristics of the loading along with the environment used to convey the stress wave. Finally, our research indicated that PO MSCs are finely tuned to respond to mechanical stimuli that fall within defined parameters.
Supervisor: Proud, William G. ; Rankin, Sara M. ; Chapman, David Sponsor: Royal British Legion
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral