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Could anti-inflammatory treatment at ACL reconstruction improve biological, functional and clinical outcomes?


Project Description

This project will test the hypothesis that inflammation after ACL reconstruction surgery is detectable in the joint fluids and blood, and reduces joint function and surgical outcomes; and that anti-inflammatory medication reduces inflammation and improves joint function and surgical outcomes.
Background to project

Osteoarthritis affects 8.5 million people in the UK and is a painful, debilitating and progressive condition with no cure apart from eventual surgical removal, fusion or replacement of the affected joint.

Osteoarthritis is commonly secondary to previous joint trauma. Such post-traumatic osteoarthritis (PTOA) accounts for ~12% of the current osteoarthritis population. Since these injuries often arise from sporting activities, individuals affected by PTOA are often affected at a young age (5-15 years after injury).

Not only does this contribute to a significant burden of pain and disability within the working age population, but existing treatments such as joint replacements are less well tolerated in this age group.

One such injury is anterior cruciate ligament (ACL) rupture of the knee, which leads to osteoarthritis in 50% of patients. Many patients will undergo ACL reconstruction surgery to stabilise the joint but, such surgery does not prevent PTOA, and may actually be detrimental due to the inflammation caused.

The project plan represents an ambitious and significant academic challenge for the knowledge base. The interactions between joint biology, joint mechanics and therapeutic outcomes are often poorly understood and difficult to measure, with few efficacy indicators.

The supervisory team applies their expertise in disease mechanisms and functional biomechanics to investigate orthopaedic conditions and thus guide improvements in patient care.
Project aims

This project aims to:

assess surgery-induced inflammation across patients at the time of ACL reconstruction by using biological, functional and clinical measures
assess whether anti-inflammatory treatments such as hyaluronan improve ACL reconstruction surgical outcomes.

This project is highly interdisciplinary, involving commercial and clinical orthopaedics, bioscience and engineering. Dr Mason and Professor Holt have developed tools and methods of assessment of joint biology and function in arthritic patients. Hospital Innovations, suppliers of specialist orthopaedic products, have successfully collaborated with Mason and Holt to investigate the relationship between biological and biomechanical indicators after knee surgery.
Key deliverables

Training in good clinical practice, human tissue act and ethics.
Patient recruitment at the time of ACL reconstruction surgery (with or without anti-inflammatory treatment, n=10/group).
Analysis of patient’s blood and synovial fluid using biological assays (eg mesoscale discovery platform for multiplex inflammatory, anabolic and catabolic mediators; ELISAs; 1H NMR spectroscopy) to assess joint health.
Analysis of biomechanical joint function, loading and muscle activity immediately prior to ACL reconstruction surgery, and again six months later.
Analysis of clinical data reflecting patient reported pain, function and quality of life.
Application of statistical tools (eg LDA, Cardiff Classifier) to reveal key diagnostic/prognostic indicators after ACL reconstruction surgery.
A toolkit of key biological and functional indicators of treatment efficacy that could be communicated to surgeons that use anti-inflammatory treatments in ACL patients.
Clinically relevant methodologies embedded into Hospital Innovations to enable them to determine the impact that anti-inflammatory treatment could have on improving patient outcomes.

Funding Notes

Residency Applicants for these awards must have a home or work address in the relevant area* of Wales (East or West) at the time of their application for funding and enrolment.
Academic criteria

Applicants for research PhDs will be expected to have one or both of the following; a first degree, normally with class 2:1 or equivalent in a relevant subject; a relevant master's degree qualification or equivalent.

How good is research at Cardiff University in Biological Sciences?

FTE Category A staff submitted: 54.70

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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