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Optimisation of osteochondral grafts for the treatment of cartilage lesions

PGR-P-982

Key facts

Type of research degree
PhD
Application deadline
Monday 31 May 2021
Project start date
Friday 1 October 2021
Country eligibility
UK only
Funding
Funded
Source of funding
Doctoral training partnership
Supervisors
Professor Ruth Wilcox
Additional supervisors
Dr Marlene Mengoni, Dr Hazel Fermor
Schools
School of Mechanical Engineering
Research groups/institutes
Institute of Medical and Biological Engineering
<h2 class="heading hide-accessible">Summary</h2>

The aim of this PhD is to evaluate osteochondral grafts for the repair of damaged cartilage in the knee. Using advanced engineering methods including finite element (FE) analysis and mechanical testing, this PhD will examine the mechanical performance of the grafts and address a pressing clinical challenge. <br /> Treatment for patients with osteoarthritis costs the NHS more than &amp;pound;5B per year, with the knee being the most common site, affecting over 4.5 million people in the UK. There is a clinical need for earlier stage, less-invasive, treatments to prevent or delay knee replacement surgery, which is costly an dnot suitable for all patients. Repair of small areas of damaged cartilage with osteochondral (cartilage + bone) grafts has shown some promise, but the clinical outcomes are variable.<br /> This PhD will use a combination of novel experimental testing and finite element (FE) modelling methods to examine the mechanical performance of osteochondral grafts, with the aim of identifying the key design features of the graft that affect performance. The study will include the use of unique in vitro testing equipment and microCT imaging facilities to examine the mechanical performance of cadaveric human and sheep knees following grafting. Image-based FE methods will be used to evaluate the graft performance, extending current methods to examine graft subsidence and damage to adjacent tissues. There will be opportunities to validate the models against both experimental data from Leeds and recent in vivo sheep studies undertaken by collaborators at UCL. The combined experimental and FE approach will be used to evaluate the effects of graft design changes, and propose how grafts can best be matched to different patient characteristics.<br /> The successful candidate should have experience in mechanical engineering methods including FE analysis and ideally have some laboratory experience. During the project, you will be expected to prepare and test human cadaveric tissue specimens; previous experience in handling human or animal tissue would be beneficial, but not essential. Full training will be provided on all laboratory methods and the associated health and safety requirements. <br /> There will be opportunities to be involved in wider activities organised by the research group, including public and patient engagement events, and bespoke training for careers in the medtech sector. You will be encouraged to develop wider skills through training provided by the University and through opportunities to participate in international conferences or laboratory visits. <br />

<h2 class="heading hide-accessible">Full description</h2>

<p><strong>Background</strong></p> <p>Osteoarthritis is estimated to affect more than 40 million people across Europe; the lifetime risk of knee osteoarthritis is estimated to be as high as 45%. While total knee replacement is used successfully to treat end-stage knee arthritis, it is an expensive procedure and is not suitable for everyone, with outcomes being poorer for younger and more active patients. The covid-19 pandemic and reductions in elective surgery have led to large increases in waiting times for knee replacements. There are therefore pressing clinical needs for earlier-stage, less invasive, treatments for knee osteoarthritis to prevent or delay the need for total knee replacement surgery. One such approach is to replace localised degeneration of the knee cartilage with an osteochondral graft, that is, a plug of healthy cartilage and underlying bone taken from another site. While some success has been reported with autologous osteochondral grafts (taken from a non-load-bearing site on the same patient), there can be issues where the tissue is extracted and this approach is not suitable for all patients. Grafts from other sources are also used clinically, or are currently under development. These include decellularised tissues (donor tissue with the cells and DNA removed to prevent immune reactions), and synthetic scaffolds. Clinical outcomes have been variable and currently little is known about the optimum graft shape or required match to the host tissue to prevent graft fibrillation or subsidence. This is partly because grafts are tested using large animal (usually sheep) models, which are not representative of the human knee, meaning devices advance to clinic without being fully optimised.</p> <p><strong>Research Objectives</strong></p> <p>This PhD will use a combination of novel experimental testing and finite element (FE) modelling methods to examine the mechanical performance of grafts in both the human and sheep joints, using <em>in vivo </em>data for validation, with the aim of identifying the key design features of the graft that affect performance. The overall objectives are:</p> <p>To use the unique <em>in vitro</em> testing equipment and microCT imaging facilities to examine the mechanical performance of cadaveric human and sheep knees following grafting.</p> <p>To build image-based FE models of the specimens to evaluate the performance of the graft, validated against the experimental data. This will extend current methods to examine graft subsidence and damage to adjacent tissues under physiological load.</p> <p>To apply the methods developed to build image-based models of sheep knees from recent <em>in vivo</em> studies, enabling the predictions to be validated against <em>in vivo</em> findings for the first time.</p> <p>To use the combination of sheep and human FE models to evaluate both the efficacy of the sheep knee model and the effects of different graft design changes, and propose how different grafts can best be matched to different patient characteristics.</p> <p><strong>Environment</strong></p> <p>The <a href="https://www.imbe.leeds.ac.uk/">Institute of Medical and Biological Engineering </a>(iMBE) at the University of Leeds is a world-renowned medical engineering research centre which specialises in research and translation of medical technologies that promote &rsquo;50 active years after 50&rsquo;. We are leading the development and testing of new treatments for knee osteoarthritis through a &pound;4million EPSRC-funded Programme Grant. Through the programme, we are developing novel methods for testing early-stage treatments in a whole natural knee <em>in vitro</em> model, as well as through image-based finite element analysis. In parallel, osteochondral grafts have been developed using a Leeds-patented decellularisation processes for use in repairing cartilage lesions. We are also collaborating with a research group at University College London on a synthetic graft they are developing.</p> <p>As a PhD student within the iMBE, you will work in a vibrant, multidisciplinary group; we have large shared offices and social space, as well as extensive grade II laboratory facilities. There will be opportunities to become involved in a variety of patient and public engagement activities, as well as group training and social events. Groups of researchers working on aligned projects or using similar methods meet regularly to share ideas and best practice, and we encourage collegiate working.&nbsp;&nbsp;We will support your long term career ambitions through bespoke training and encourage external secondments, laboratory visits or participation at international conferences.</p>

<h2 class="heading">How to apply</h2>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="http://www.leeds.ac.uk/rsa/prospective_students/apply/I_want_to_apply.html">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is <em>Optimisation of osteochondral grafts for the treatment of cartilage lesions</em> as well as&nbsp;<a href="https://eps.leeds.ac.uk/staff/192/Professor_Ruth_Wilcox">Professor Ruth Wilcox </a>as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

<h2 class="heading heading--sm">English language requirements</h2>

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

<h2 class="heading">Funding on offer</h2>

<hr /> <p>A highly competitive EPSRC Doctoral Training Partnership Studentship consisting of the award of fees with a maintenance grant of &pound;15,609&nbsp;per annum&nbsp;for session 2021/22&nbsp;for 3.5 years.<br /> <br /> This opportunity is open to UK applicants only. All candidates will be placed into the EPSRC Doctoral Training Partnership Studentship Competition and selection is based on academic merit.</p> <p>The&nbsp;<a href="https://www.ukcisa.org.uk/"><font color="#0066cc">UKCISA</font></a>&nbsp;website will be updated in due course with information regarding Fee Status for Non-UK Nationals starting from September/October 2021.</p>

<h2 class="heading">Contact details</h2>

<p>For informal queries&nbsp;regarding this project, please contact Professor Ruth Wilcox at e:&nbsp;<a href="mailto:EMAIL@leeds.ac.uk"><font color="#0066cc">r.k.wilcox@leeds.ac.uk</font></a></p> <p>For further information regarding your application,&nbsp;please contact Doctoral College Admissions<br /> e:&nbsp;<a href="mailto:phd@engineering.leeds.ac.uk">phd@engineering.leeds.ac.uk</a> t: +44 (0)113 343 5057.</p>


<h3 class="heading heading--sm">Linked funding opportunities</h3>
<h3 class="heading heading--sm">Linked research areas</h3>