Theranostic doubly crosslinked microgels: From a new materials class to an injectable load supporting medical device

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Degeneration of the intervertebral disc (DIVD) and osteoarthritis (OA) result in chronic pain. They are major UK healthcare problems that are projected to grow as society ages, leading to reduced productivity and increased NHS costs. Double crosslinked microgels (DX MGs) are load supporting gels made from pre-formed microgel (MG) particles that can be linked together in vivo. MG particles are crosslinked polymer colloid particles that swell when the pH approaches the pKa of the polymer. My previous EPSRC-funded DX MG research established the concept of injectable biocompatible DX MGs for restoring the mechanical properties of degenerated IVDs. Recently we have shown that injectable DX MGs are a potential treatment for DIVD. Unfortunately, like all gels, our first generation DX MGs cannot provide optimal stress distributions throughout degenerated IVDs due to the complex, irregular shape of the voids that they fill. Unfortunately, there is no possibility of external tuning of the load distributions once injected. Achieving optimal load support will give the best pain relief and prevent further degeneration. This goal requires new gels with externally controlled compressive strain tuning abilities which can be informed by the strain present in vivo. In this proposal I plan to establish next generation theranostic DXMGs which provide therapeutic (load support) benefit and diagnostic strain information from within IVDs. I plan to construct new DX MGs that use deeply penetrating near-infrared (NIR) light, i.e., NIR DX MGs. These new injectable gels will report their mechanical environment in vivo and enable this to be tuned and optimised remotely. NIR DX MGs will also be photo-degradable which will enable their light-guided replacement by native tissue. My proposed theranostic NIR DX MGs are a new materials class that will act as an injectable load supporting medical device. A successful outcome will enable personalised, low cost, load supporting soft tissue repair.