Historically, bone defects resulting from trauma, disease or infection are treated with autograft or allograft. Autograft is bone transplanted from a non-critical area of the skeleton and allograft is bone donated from another member of the same species. The drawbacks with these treatments such as limited availability, donor site morbidity, high cost and disease transmission have driven increasing use of bone graft substitute (BGS) materials. These represent 15% of the £1.6 billion global orthobiologics market. BGS materials available to date are not suitable for use in grafts that are intrinsic to the stability of the skeleton. Thus, the aim for this project was to fabricate an off the shelf and economically viable BGS that will support the skeletal structure whilst healing occurs. This project employed an empirical approach utilising both rapid prototyping (RP) and conventional manufacturing processes to produce novel BGSs. A range of RP techniques were attempted and discovered to be unsuitable as a result of their long build and postprocessing times, poor availability of suitable materials, and undesirable surface finish. Experiments with injection moulding and laser drilling of polylactic acid (PLA) successfully produced 10 mm blocks with a compressive strength of 67 – 80 MPa and compressive modulus of 1.5 – 2.2 GPa. This line of research led to the hypothesis that ceramic extrusion, a process hitherto untested for use in bone tissue engineering (BTE), may be feasible for production of a novel and high strength BGS. In collaboration with an international expert in the manufacture of ceramic monoliths it was possible, for the first time, to manufacture hydroxyapatite (HA) monoliths by adapting the process used for manufacture of automotive exhaust catalysts. These HA monoliths exhibited a compressive strength of 142 – 265 MPa and compressive modulus of 3.2 – 4.4 GPa. The exceptional strength of these monoliths match the properties of cortical bone whilst retaining the high levels of porosity (> 60 %) found in cancellous bone. This combination of strength and porosity will enable treatment of large structural bone defects where the high strength will withstand typical skeletal forces whilst the high porosity allows blood vessels to infiltrate the monolith and begin the healing process. Furthermore, these HA monoliths support the proliferation and differentiation of human osteoblast-like MG63 cells and compare very favourably with a market leading BGS material in terms of their biological performance. It is suggested that this work will result in the development of a new family of high strength and high porosity BGSs for use in challenging clinical situations. The International Preliminary Examination Report for the patent issued to the author (WO 2007/125323) decreed that all 45 claims contained novelty and an inventive step. Two successful applications for research funding have raised nearly £50,000 that helped fund this research effort. Warwick ventures are currently involved in negotiating with medical partners to licence this technology for clinical use.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:537771 |
| Date | January 2009 |
| Creators | Meredith, James O. |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/36741/ |
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