The project described in this application is concerned with developing a minimally invasive method of repairing degenerate intervertebral discs. The intervertebral discs have a mechanical function; they are the joints of the spine and support the high lo ads arising from body weight and muscle activity; maintaining high water content is essential for their function. The ability of the discs to remain hydrated under load is determined principally by the large proteoglycan aggrecan which generates a very hi gh osmotic pressure on account of its charge properties. Discs degenerate early; aggrecan is degraded and lost from the central region of the disc which thus loses its load-bearing capacity. Degenerate intervertebral discs are strongly associated with b ack pain; severe back pain affects a significant proportion of the population and is one of the most expensive of chronic disorders in western societies. At present the only treatments on offer are palliative or surgical; surgery is expensive and invasiv e with long recovery times. Here we propose an alternative method of repairing discs using new synthetic biomaterials based on charged hydrogels already in use for treatment of corneal-defects. The novelty of the proposal is that (a) treatment to introd uce the synthetic biomaterial into the disc will be only minimally invasive and so costly and expensive surgery will be avoided (b) the biomaterial will polymerise in situ, be non-toxic and bond to the healthy surrounding discs (c) the biomaterial will be engineered to mimic the physico-chemical behaviour of healthy disc tissue and so will restore disc biomechanical function. The work will involve (i) characterising factors regulating aggrecan osmotic and hydraulic permeability properties using state-of-a rt techniques (ii) manipulating charge density, chain length and branching of hydrogels to mimic relevant aggrecan properties (iii) in-situ polymerization of the hydrogel monomers in disc explants.
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