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Title: Bone tissue engineering : harnessing interdisciplinary approaches for clinical application
Author: Smith, James Oliver
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2013
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There is an acute requirement for novel clinical approaches to combat loss or dysfunction of skeletal tissue. Inherent disadvantages of current reconstructive strategies combined with the ageing population and a continuing increase in musculoskeletal pathology and patient expectations, highlight a pressing need to augment current practice with osteoregenerative techniques. Tissue engineering shows promise as a discipline to meet these needs by the systematic selection and manipulation of cells, matrices and biological stimuli to produce the required tissue. This thesis examines current and emerging clinical strategies available for replacement of skeletal tissue and discusses the requisite properties that novel approaches are required to possess before successful progress to clinical application can be achieved. Each chapter in this thesis details a specific aspect of the continuous process in the development of a novel tissue engineering strategy, considering also the wider scientific, logistical, clinical, financial and practical issues that must be addressed for successful outcomes: • The effects of cells, cytokines and material properties are explored in the context of recreating normal biological structure and function. • The limitations of current clinical cell enrichment techniques are discussed and a novel intra-operative strategy is shown to enrich skeletal stem cells from bone marrow by acoustic filtration, suitable for potential orthopaedic application. • A tissue engineering approach applied to an established orthopaedic implant (Tantalum Trabecular Metal) is shown to support osteogenic differentiation and enhance bone-implant interface strength, with potential clinical applicability. • A murine model for skeletal regeneration is used to evaluate a novel ternary polymer blend scaffold for efficacy in a tissue engineering approach. • An ovine model for skeletal regeneration is defined and evaluated along with a candidate binary polymer blend scaffold for tissue engineering strategies. • Many of the hurdles to successful clinical translation that are commonly overlooked are discussed with particular reference to the cellular toxicity of local anaesthetics. This thesis demonstrates the considerable potential of skeletal tissue engineering approaches, but highlights the requirement for a concerted multidisciplinary appreciation to achieve successful clinical translation.
Supervisor: Oreffo, Richard ; Dunlop, Douglas Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General) ; TA Engineering (General). Civil engineering (General)