Investigating the tissue response to a novel knee ligament implant

This full-time DPhil (PhD) post at the Botnar Institute, NDORMS, University of Oxford, will use cutting edge biomaterial and biological characterisation methods to investigate the tissue response to a novel knee ligament implant in vivo and ex vivo. You will work as part of a collaborative, interdisciplinary team who will provide an exciting range of training opportunities.

Anterior Cruciate Ligament (ACL) tears affect an estimated 20,000 people per year in the UK, the majority of which are teenagers and young adults. These injuries can cause a profound reduction in quality of life and decrease physical activity. Furthermore, they increase the risk of osteoarthritis in an otherwise young and fit patient population. Around 80% of cases require surgery and these are typically done through reconstruction. ACL reconstruction (ACLR) often utilises autografts such as hamstring grafts. Although ACLR with autografts aims to restore knee stability, it suffers from limited donor-site availability, consequent harvest-site morbidity and re-rupture in 15% of cases. Postoperative pain management using injections of anestethics and various drug combinations, is common.

To replace the need for autografts and improve patient outcomes, we have developed a unique synthetic braided cord made from polycaprolactone, a degradable polymer, that can be used with existing fixation devices and techniques in ACLR. The device can stabilise the knee mechanically and is designed to encourage tissue repair. It is made by electrospinning to mimic the healthy structure of the extracellular matrix of ACL and provide physical cues that stimulate tissue infiltration from the torn tissue ends.

We plan to demonstrate its safety and efficacy in an ovine study set to begin in 2025, with the anticipated data supporting a future application for a clinical safety trial, marking a key step in this highly translational project.

The envisioned 3-years PhD project will build upon this work and will involve three key objectives:

1. Perform an in-depth analysis of the data collected during the ovine study, including studying cell populations, extracellualr matrix (ECM) deposition, and the immune response (macrophages, foreign body giant cells, etc.) to the device – including single-nuclei sequencing;
2. Carry out further ex-vivo work with human tissue explants to identify key cell populations driving the biological response to the device and compare these metrics with the in vivo study;
3. Develop new device design variants, such as involving bioactive coatings, and study the effects of the new features on in-vitro cell response to primary human cells.

SCHOLARSHIP:

This is a fully-funded 3-year DPhil project, supported by the Norman Collisson Foundation. The scholarship covers the equivalent of UK tuition fees and provides a stipend to support living costs. If you are applying as an overseas candidate, you must be able to cover the difference between home and overseas fees. The successful candidate will be associated with Linacre College.

KEYWORDS:

electrospinning, ACL repair, artificial ligament, polycaprolactone, in vivo/ex vivo immunoresponse

SUPERVISORY TEAM AND RESEARCH GROUPS:

The supervisory team will consist of Associate Professor Pierre Mouthuy, Dr Kaili Chen, Associate Professor Sarah Snelling and Dr Mathew Baldwin, to cover the expertise related to bioengineering, materials, biology and clinical sciences, respectively. They will provide you with essential oversight and support for the laboratory, engineering, computational and clinical aspects of your DPhil.

You will join our interdisciplinary and collaborative research teams of postdoctoral scientists (both laboratory and computational), clinical academics, research assistants and DPhil students. This will be enriched by regular supervisory and weekly lab team meetings.

Relevant links:

• Mouthuy group: www.ndorms.ox.ac.uk/research/research-groups/mouthuy-group-soft-tissue-engineering
• Snelling group: www.ndorms.ox.ac.uk/research/research-groups/snelling
• Mathew Baldwin: https://www.ndorms.ox.ac.uk/team/matthew-baldwin
• Kaili Chen: https://www.ndorms.ox.ac.uk/team/kaili-chen

TRAINING:

The Botnar Research Centre - part of Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS) - plays host to the University of Oxford's Institute of Musculoskeletal Sciences, which leads research and education into the causes of musculoskeletal diseases and their treatments.

We will ensure hands-on laboratory and computational training and embedding within our international single-cell sequencing network which is led by the Snelling team. This will provide the candidate with research guidance and support both locally with our expert team and through virtual interactions with our international collaborators. Finally, the student will be expected to regularly present data in Departmental seminars, laboratory group meetings and large project group meetings. In particular students will have the opportunity to work closely with the BioLig project team, a large network of collaborators including engineers, biologists, clinicians, veterinarians, statisticians and regulatory experts.

A core curriculum of lectures will be taken in the first term to provide a solid foundation in a broad range of subjects including musculoskeletal biology, inflammation, epigenetics, translational immunology, bioengineering, data analysis and the microbiome. 

Students will have access to various courses run by the Medical Sciences Division (MSD) Skills Training Team and other Departments within the MSD. All students are required to attend a 2-day Statistical and Experimental Design course at NDORMS that is run by the IT department (information will be provided once accepted to the programme).

HOW TO APPLY:

You should contact Associate Professor Pierre Mouthuy or NDORMS Graduate Studies (graduate.studies@ndorms.ox.ac.uk). 

Interested applicants should have, or expect to obtain, a first or upper second-class BSc degree or equivalent in a relevant subject and will also need to provide evidence of English language competence (where applicable). The online application guide can be accessed here and the DPhil will commence in October 2025. 

Applications should be made to the following programme, using the specified course code:

D.Phil in Musculoskeletal Sciences (course code: RD_ML2)

Reference Code: NDORMS 2025/NCF Scholarship

For further information, please visit http://www.ox.ac.uk/admissions/graduate/applying-to-oxford.