Towards Repairing Degenerated Intervertebral Discs using pH-Responsive Microgels

椎间盘退变（DIVD）是导致IVD内产生互连空隙的过程。空隙导致椎间盘高度降低和慢性腰痛。DIVD对社会有重大的不利影响。2004年，由于美国生产力损失，DIVD的估计成本为400亿美元。目前DIVD的脊柱治疗涉及大手术干预，恢复时间延长。目前迫切需要一种能够恢复椎间盘高度的微创DIVD治疗。在我们的12个月可行性研究（GR/S75819/01）中，结果表明，在生物力学负荷下，将pH响应性微凝胶分散体注射到退化的IVD中可以将椎间盘高度恢复到正常值。微凝胶是pH响应性聚合物胶体颗粒，当颗粒电荷增加时其膨胀。在退化的IVD中，它们可以通过pH值触发形成物理凝胶。本延续提案旨在研究物理胶凝微凝胶支持IVD负载的原理，并将工作扩展到研究共价连接的微凝胶颗粒凝胶。本研究旨在提供一套设计规则，使未来的临床开发的注射微凝胶修复系统的DIVD。

Degeneration of the intervertebral disc (DIVD) is a process that results in generation of interconnected voids within IVDs. The voids result in a loss of disc height and chronic low back pain. DIVD has a major adverse effect on society. The estimated cost of DIVD due to lost productivity in the US in 2004 was $USD 40 billion. Current spinal therapy for DIVD involves major surgical intervention with protracted recovery times. There is an urgent need for a minimally invasive DIVD treatment that restores disc height. In our 12 month feasibility study (GR/S75819/01) it was shown that injection of a pH-responsive microgel dispersion into a degenerated IVD could restore the disc height to normal values under biomechanical loads. Microgels are pH-responsive polymer colloid particles that expand when the particle charge increases. They can be triggered to form physical gels using pH within degenerated IVDs. This continuation proposal seeks to investigate the principles underpinning IVD load support by physically gelled microgels and extend the work to study covalently-linked microgel particle gels. This study seeks to deliver a set of design rules that will enable future clinical development of an injectable microgel repair system for DIVD.