Development of an innervated in vitro Osteoarthritis Model for Drug Discovery and Drug Screening

骨关节炎(OA)是一种疼痛和致残性的关节疾病。它主要影响手、臀部和膝盖，在大多数国家非常常见。据估计，超过2.5亿人患有骨关节炎，这对全球经济和医疗体系产生了重大影响。骨关节炎是英国最常见的关节炎形式，约有三分之一的45岁及以上人群受到影响(约875万人)。在接下来的10年里，随着我们寿命的延长，骨关节炎患者的数量预计将大幅上升，与骨关节炎相关的肥胖病例也在增加。目前，大多数骨性关节炎的治疗仅限于缓解疼痛。市场上没有任何药物可以逆转这种疾病，甚至阻止其发展。最终，大多数患者需要进行全关节置换术。由于骨关节炎是一种复杂的疾病，涉及关节中许多不同类型的细胞和组织，因此寻找和测试治疗骨关节炎的新药非常复杂，因为很难在实验室复制骨关节炎。我们的项目将推进包括神经细胞在内的骨关节炎的开发模型，以评估对控制疾病至关重要的新型止痛药物，评估药物在治疗疾病中的有效性，并帮助取代新的骨关节炎疗法的动物试验。模型中的组织代表了人类关节、骨骼和软骨的不同部分，这些部分将被神经细胞打印出来，产生骨关节炎的3D模型。化合物将激活疾病过程，包括神经激活，并将引入药物来评估它们阻止或逆转骨关节炎和疼痛敏感化的能力。我们的模型将推进有效的骨关节炎药物的识别，在现有的实验室测试和当前的小动物模型的基础上显著改进。

Osteoarthritis (OA) is a painful and disabling disease of the joints. It principally affects the hands, hips and knees and is very common in most countries. It is estimated that over 250 million people have osteoarthritis which has a significant impact on global economies and healthcare systems. Osteoarthritis is the most common form of arthritis in the UK, (around 8.75 million) affecting around a third of people aged 45 and over. Within the next 10 years, the number of people with osteoarthritis is predicted to rise substantially as we are living longer and cases of obesity, which is linked to osteoarthritis, are also increasing. Currently, most treatments for osteoarthritis are restricted to pain relief. There are no drugs on the market that can reverse the disease or even halt its progression. Ultimately, most patients require a total joint replacement. Since osteoarthritis is a complex disease, involving many different types of cells and tissues in the joint, finding and testing new drugs to treat osteoarthritis is very complex as it is difficult to replicate osteoarthritis in the laboratory. Our project will advance a developed model of osteoarthritis to include nerve cells in order to assess novel pain-relieving drugs, vital for the control of the disease, assess the effectiveness of drugs in treating the disease and aid in the replacement of animal testing for new osteoarthritis therapies. The tissues within the model represent different parts of a human joint, bone and cartilage which will be "printed" with nerve cells, producing the 3D model of osteoarthritis. Compounds will activate the disease process, including neural activation and drugs will be introduced to evaluate their ability to stop or reverse osteoarthritis and pain sensitisation. Our model will advance the identification of effective osteoarthritis drugs, improving significantly on existing laboratory tests and current small animal models.