Skeletal stem cell based therapies offer tremendous potential for regeneration of a patient's bone. With the demo graphics of an ageing population, the demand for skeletal reconstruction to replace lost or damaged bone is expanding dramatically. Novel bone tissue engineering techniques offer the opportunity to push the boundaries of bone regeneration, yet few strategies have been translated to clinical practice. This thesis aims to explore novel bone regeneration strategies in vitro and in vivo, and details the clinical application of those techniques. The effects of skeletal stem cells, growth factors and material properties on osteogenesis of bone tissue engineering constructs were explored: • Skeletal stem cells and human fibronectin were shown to augment the biomechanical characteristics of impacted allograft. • Alteration of porosity in a synthetic ceramic scaffold had an effect on osteogenesis. • Innovative technology for enriching the skeletal stem cell fraction from aspirated bone marrow was successfully trialled on bone marrow from an elderly COhOli of . patients, reaching a therapeutic cellular concentration. • A pathological role for osteogenic cells was demonstrated in unicameral bone cysts, with up-regulation of RANI<L related cytokines and stimulation of osteoclastic activity. • Retrieval of tissue from an early translated tissue engineering case provided the oppOliunity for ex vivo analysis, with discussion on lessons that can be learned for future translation. • A novel tissue engineering strategy, to augment the biological and mechanical characteristics of impacted allograft, was subsequently translated to a case series of four patients with avascular necrosis of the femoral head. Surgical technique, clinical follow-up and analysis of retrieval tissue is described. This study has shown the efficacy of skeletal stem cells for bone regeneration in vitro and in vivo, and explored techniques to further augment their osteogenic capacity on bone graft extenders. The translational potential of this bone tissue engineering technology has been realised from the bench to the clinic.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:595528 |
| Date | January 2011 |
| Creators | Aarvold, Alexander |
| Contributors | Oreffo, Richard ; Dunlop, Douglas |
| Publisher | University of Southampton |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://eprints.soton.ac.uk/362817/ |
Page generated in 0.0011 seconds