Nanostructured gels for intervertebral disc load support and directed regeneration

下背痛是英国一个主要且日益严重的医疗保健问题。它造成发病率，并因雇员缺勤而大大降低国家生产力。下背痛的一个主要原因是椎间盘退变（DIVD）。DIVD最常见的治疗方法是脊柱融合术，这是一种具有不同患者结局的主要外科手术。原则上，提供负载支持同时允许组织再生的可注射凝胶可以为DIVD提供非手术的、具有成本效益的治疗。我们的目标是建立一种可注射的合成共聚物凝胶，提供即时的负荷支持（以减轻疼痛），然后生物降解，由再生组织取代。一种非生物降解的可注射凝胶技术，由美国开发。曼彻斯特队为退化的IVD提供了负载支持。然而，这些凝胶在高应变（低延展性）下断裂，并且不能重建椎间盘（IVD）内的天然细胞外基质（ECM）的纳米级结构特征。此外，它们不能支持组织再生。在拟议的工作计划中，我们将通过将新的各向异性嵌段共聚物蠕虫状颗粒与新的pH响应性纳米凝胶颗粒相结合来设计新型可注射仿生凝胶，以产生人类IVD内ECM的纳米级特征。这种纳米结构的凝胶应该具有改善的延展性，并提供负载支持和适当的物理/生物线索以指导ECM合成和组织生长。此外，它们将被设计为生物降解，并逐渐被再生组织所取代。一个成功的结果将建立一个新的家庭注射合成共聚物凝胶，应使非手术治疗DIVD更接近现实。

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.