Engineering next generation bioresponsive biopolymers: mimetic cartilage proteoglycans

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Osteoarthritis and rheumatoid arthritis (OA and RA) are painful joint diseases caused by the breakdown of the shock absorbing and lubricating layer of tissue covering the ends of bones in joints. Over 8.5M people in the UK have OA and prevalence increases with age. Currently, in addition to treatment with anti-inflammatory medicines, a thick fluid can be injected directly into arthritic joints to temporarily replace the thick, gel-like substance that normally cushions the joint (but is lost in arthritis) to improve joint lubrication, reduce pain, improve mobility, and improve activity. However, many patients experience pain from repeated injections, which have to be given at regular intervals because the body's own proteins breaks down the gel-like substance. Here, we will develop a modular platform to produce well-defined treatments that combine anti-inflammatory drugs with joint lubricating substances to reduce pain and swelling in arthritic joints. This controllable assembly will enable us to tailor the composition, thickness, duration of action and allow us to combine multiple treatments in one construct.In this project, we will first chemically join specific sugar molecules into short chains, then attach them along the length of a longer polymer chain to mimic the substances naturally found inside joints. We will then study the biological effects of these tailored constructs using cartilage grown in the laboratory. If successful, we will apply this platform approach to treat other diseases and incorporate different drugs.