Engineering next generation bioresponsive biopolymers: mimetic cartilage proteoglycans

骨关节炎和类风湿性关节炎(OA和RA)是由覆盖在关节骨端的组织的减震和润滑层破裂引起的疼痛的关节疾病。在英国，超过850万人患有骨性关节炎，而且患病率随着年龄的增长而增加。目前，除了使用消炎药治疗外，还可以将稠密的液体直接注射到关节炎关节中，暂时取代通常缓冲关节(但在关节炎中消失)的稠密凝胶状物质，以改善关节润滑，减轻疼痛，改善活动能力。然而，许多患者会因为重复注射而感到疼痛，因为人体自身的蛋白质会分解这种凝胶状物质，所以必须定期注射。在这里，我们将开发一个模块化平台，以生产定义明确的治疗方法，将抗炎药物与关节润滑物质相结合，以减轻关节炎关节的疼痛和肿胀。这种可控制的组装将使我们能够定制成分、厚度和作用时间，并允许我们在一个结构中结合多种处理。在这个项目中，我们将首先将特定的糖分子化学连接到短链中，然后沿着较长的聚合链的长度将它们连接起来，以模拟关节内自然存在的物质。然后，我们将使用实验室中生长的软骨来研究这些量身定做的结构的生物学效应。如果成功，我们将应用这个平台的方法来治疗其他疾病，并整合不同的药物。

Osteoarthritis and rheumatoid arthritis (OA and RA) are painful joint diseases caused by the breakdown of the shock absorbing and lubricating layer of tissue covering the ends of bones in joints. Over 8.5M people in the UK have OA and prevalence increases with age. Currently, in addition to treatment with anti-inflammatory medicines, a thick fluid can be injected directly into arthritic joints to temporarily replace the thick, gel-like substance that normally cushions the joint (but is lost in arthritis) to improve joint lubrication, reduce pain, improve mobility, and improve activity. However, many patients experience pain from repeated injections, which have to be given at regular intervals because the body's own proteins breaks down the gel-like substance. Here, we will develop a modular platform to produce well-defined treatments that combine anti-inflammatory drugs with joint lubricating substances to reduce pain and swelling in arthritic joints. This controllable assembly will enable us to tailor the composition, thickness, duration of action and allow us to combine multiple treatments in one construct.In this project, we will first chemically join specific sugar molecules into short chains, then attach them along the length of a longer polymer chain to mimic the substances naturally found inside joints. We will then study the biological effects of these tailored constructs using cartilage grown in the laboratory. If successful, we will apply this platform approach to treat other diseases and incorporate different drugs.