Nanostructured gels for intervertebral disc load support and directed regeneration

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Lower back pain is a major and growing healthcare problem in the UK. It causes morbidity and significantly reduces national productivity through employee absence. A major cause of lower back pain is degeneration of the intervertebral disc (DIVD). The most common treatment for DIVD is spinal fusion, which is a major surgical procedure with variable patient outcome. In principle, injectable gels that provide load support while allowing tissue regeneration can provide a non-surgical, cost-effective therapy for DIVD. We aim to establish an injectable synthetic copolymer gel that provides immediate load support (to alleviate pain) and then biodegrades to be replaced by regenerated tissue. A non-biodegradable injectable gel technology developed by the U. Manchester team has provided load support for degenerated IVDs. However, these gels fracture at high strain (low ductility) and do not recreate the nanometre-scale structural features of the natural extracellular matrix (ECM) within the intervertebral disc (IVD). Moreover, they were not able to support tissue regeneration. In the proposed work programme, we will design novel injectable biomimetic gels by combining new anisotropic block copolymer worm-like particles with new pH-responsive nanogel particles in order to produce the nanometre-scale features that are characteristic of the ECM within human IVDs. Such nanostructured gels should have improved ductility and provide both load support and the appropriate physical / biological cues to direct ECM synthesis and tissue growth. Furthermore, they will be designed to biodegrade and be gradually replaced by regenerated tissue. A successful outcome will establish a new family of injectable synthetic copolymer gels that should bring non-surgical therapies for DIVD closer to reality.