Meredith, James O. (2009) Biocomposites for bone tissue engineering : innovation report. EngD thesis, University of Warwick.

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Abstract

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.

Item Type:	Thesis or Dissertation (EngD)
Subjects:	R Medicine > RD Surgery T Technology > TA Engineering (General). Civil engineering (General)
Library of Congress Subject Headings (LCSH):	Bone-grafting, Bone substitutes
Official Date:	February 2009
Dates:	Date Event February 2009 Submitted
Institution:	University of Warwick
Theses Department:	School of Engineering
Thesis Type:	EngD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Mallick, Kajal Kanti, 1956- ; Neailey, Kevin
Sponsors:	Engineering and Physical Sciences Research Council (EPSRC) ; Spinner (Firm) ; Warwick Innovative Manufacturing Research Centre
Extent:	120 leaves
Language:	eng

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