Towards Repairing Degenerated Intervertebral Discs using pH-Responsive Microgels

椎间盘退变(DIVD)是一种导致IVD内相互连接的空洞产生的过程。空洞会导致腰椎间盘高度降低和慢性下腰痛。DIVD对社会有很大的不利影响。2004年，美国因生产力丧失而造成的DIVD成本估计为400亿美元。目前治疗DIVD的脊柱疗法主要是手术治疗，且恢复时间较长。迫切需要一种恢复椎间盘高度的微创DIVD治疗。在我们12个月的可行性研究(GR/S75819/01)中，研究表明，在生物力学载荷下，向退变的IVD内注入pH响应型微凝胶分散体可以将椎间盘高度恢复到正常值。微凝胶是一种对pH敏感的聚合物胶体颗粒，当颗粒电荷增加时会膨胀。它们可以被触发，在退化的IVD中使用pH形成物理凝胶。这项继续提案旨在研究物理凝胶微凝胶支持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。这项研究试图提供一套设计规则，使DIVD可注射微凝胶修复系统的未来临床开发成为可能。

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.