Theranostic doubly crosslinked microgels: From a new materials class to an injectable load supporting medical device

椎间盘退行性变(DIVD)和骨关节炎(OA)会导致慢性疼痛。它们是英国的主要医疗问题，预计将随着社会老龄化而增加，导致生产率下降和NHS成本增加。双交联型微凝胶(DX MG)是由预先形成的微凝胶(MG)颗粒制成的负载凝胶，可以在体内连接在一起。镁颗粒是一种交联的聚合物胶体颗粒，当pH接近聚合物的pKa时会膨胀。我之前的EPSRC资助的DX MG研究确立了可注射生物相容DX MG的概念，用于恢复退行性IVD的机械性能。最近，我们发现可注射的DX-MG是治疗DIVD的一种潜在方法。不幸的是，像所有凝胶一样，我们的第一代DX MGs由于填充的空洞形状复杂、不规则，无法在退化的IVD中提供最佳的应力分布。不幸的是，一旦注入，就不可能对负载分布进行外部调整。获得最佳的负荷支持将提供最好的疼痛缓解和防止进一步退化。要实现这一目标，需要具有外部控制的压缩应变调节能力的新凝胶，这种能力可以通过体内存在的应变来了解。在这项提案中，我计划建立下一代治疗性DXMG，从IVDS内提供治疗(负荷支持)益处和诊断应变信息。我计划构建使用深度穿透近红外(NIR)光的新型DX MGs，即近红外DX MGs。这些新的可注射凝胶将报告它们在体内的机械环境，并使之能够远程调整和优化。NIR DX MG也将是可光降解的，这将使它们的光导替换为自然组织。我提出的治疗近红外DX MG是一种新的材料类别，它将作为一种可注射的负载支撑医疗设备。成功的结果将使个性化、低成本、负重支持软组织修复成为可能。

Degeneration of the intervertebral disc (DIVD) and osteoarthritis (OA) result in chronic pain. They are major UK healthcare problems that are projected to grow as society ages, leading to reduced productivity and increased NHS costs. Double crosslinked microgels (DX MGs) are load supporting gels made from pre-formed microgel (MG) particles that can be linked together in vivo. MG particles are crosslinked polymer colloid particles that swell when the pH approaches the pKa of the polymer. My previous EPSRC-funded DX MG research established the concept of injectable biocompatible DX MGs for restoring the mechanical properties of degenerated IVDs. Recently we have shown that injectable DX MGs are a potential treatment for DIVD. Unfortunately, like all gels, our first generation DX MGs cannot provide optimal stress distributions throughout degenerated IVDs due to the complex, irregular shape of the voids that they fill. Unfortunately, there is no possibility of external tuning of the load distributions once injected. Achieving optimal load support will give the best pain relief and prevent further degeneration. This goal requires new gels with externally controlled compressive strain tuning abilities which can be informed by the strain present in vivo. In this proposal I plan to establish next generation theranostic DXMGs which provide therapeutic (load support) benefit and diagnostic strain information from within IVDs. I plan to construct new DX MGs that use deeply penetrating near-infrared (NIR) light, i.e., NIR DX MGs. These new injectable gels will report their mechanical environment in vivo and enable this to be tuned and optimised remotely. NIR DX MGs will also be photo-degradable which will enable their light-guided replacement by native tissue. My proposed theranostic NIR DX MGs are a new materials class that will act as an injectable load supporting medical device. A successful outcome will enable personalised, low cost, load supporting soft tissue repair.