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Details of Grant 

EPSRC Reference: EP/W021234/1
Title: Osteoarthritic cartilage regeneration using a combination of tough biomaterials and nanotechnology-enabled gene therapy.
Principal Investigator: Oliva-Jorge, Dr N
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Bioengineering
Organisation: Imperial College London
Scheme: New Investigator Award
Starts: 01 April 2022 Ends: 30 September 2024 Value (£): 425,888
EPSRC Research Topic Classifications:
Biomaterials Biomechanics & Rehabilitation
EPSRC Industrial Sector Classifications:
Healthcare
Related Grants:
Panel History:
Panel DatePanel NameOutcome
16 Feb 2022 Healthcare Technologies Investigator Led Panel Feb 2022 Announced
Summary on Grant Application Form
Osteoarthritis is a musculoskeletal condition where cartilage - the rubber-like padding that protects the ends of bones at the joints - becomes damaged due to wear and tear, causing debilitating pain. Around 1 in 3 people in the UK over 45 years of age (8.75 million) have actively sought treatment for osteoarthritis, and 80% of the population suffers it by age 65. Studies have shown that human cartilage experiences no significant replacement in adult life. The main reason for this is a lack of blood supply to the joints: without nutrients, chondrocytes (cells present in the joints) cannot grow or make more cartilage. Hence, as we age, more cartilage gets irreversibly damaged, eventually leading to bone rubbing against bone.

Biomaterials present an ideal strategy to regenerate cartilage, as they can offer a scaffolding for chondrocytes to proliferate, while acting as a depot for medicine to heal cells. However, some challenges exist. First, studies have showed that cartilage changes when the joint is affected by OA, and that its mechanical properties need to be returned to pre-arthritic levels before chondrocytes can grow new healthy cartilage. Moreover, OA-associated changes also lead to decreased efficacy of drugs. This is a difficult challenge, which requires the biomaterial scaffold to mimic the natural mechanical properties of cartilage for the body's natural healing process to work effectively, as well as enhance the efficacy of any therapeutic interventions. This also means that we can now expand the potential of biomaterials to advance beyond mere cartilage replacement to actual cartilage regeneration. Ideally, an optimal biomaterial must also be injectable to allow a minimally invasive delivery procedure, as opposed to open surgery. It is also important that the biomaterial scaffold must be loaded with drugs to treat inflammation. Recent studies have pointed at gene therapy as a promising approach to restore defective genes in chondrocytes that trigger an inflammatory response and consequent destruction of cartilage. However, the delivery of genes inside chondrocytes is very challenging and hampers the development of these therapies. My group has developed nanoparticles that can, for the first time, deliver genes inside chondrocytes, overcoming the current limitations of gene therapy in OA treatment.

The overall aim of this project is to combine a cartilage-mimicking biomaterial with nanoparticle-enabled gene therapy to promote simultaneous OA treatment and new cartilage production. The individual objectives are:

1. Cartilage Replacement: Develop biomaterials that mimic the compression forces of cartilage and are injectable and biocompatible.

2. Cartilage Regeneration: Study the effects of biomaterials on cartilage production.

3. Osteoarthritis treatment: Combine a regenerative biomaterial with gene therapy to simultaneously treat inflammation and promote cartilage regeneration in OA.

The main application of this research lies on the development of new therapies for OA and cartilage regeneration. The benefits of such a technology will have a tremendous economic and social impact. Chronic pain leads to reduced mobility in patients, which has an impact both physically (60% increase in obesity, 3-fold increase of cardiovascular disease) and mentally (social isolation and loss of independence). A recent report estimated that OA will cost the NHS over £100 billion over the next decade, mostly due to the lack of efficient therapies. The chronic aspect of OA has an added impact on the economy, with 36 million workdays lost with a loss of economic production of over £3.2 billion and over £200 million spent on social services. OA is the most common condition for Disability Living Allowance (DLA), with the staggering statistic of only 1 in 200 people on benefits returning to work. It becomes clear from these numbers that this research is impactful and timely.

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Organisation Website: http://www.imperial.ac.uk