Manufacturing development of an orthopaedic knee implant for total meniscus replacement incorporating a novel load-bearing hydrogel

在英国，每年有超过400万人受到半月板缺陷引起的疼痛和不动的影响，成本相当于国民生产总值的1%（NHS商业计划2017）。该问题不仅限于与年龄相关的退行性疾病，还包括任何年龄段患者的事故/运动损伤。开发具有适合此类软组织矫形应用的表面特性的承重材料的技术挑战限制了治疗选择。在没有替代器械的情况下，不可修复半月板的标准治疗是部分或完全切除（半月板切除术），全球每年有200万例此类手术（Li 2020）。作为回应，伦敦帝国理工学院的SME分拆公司Orthonika开发了用于半月板置换的新型增强型承重PVA-PEG水凝胶材料。这些独特的材料通过可靠和成熟的方法直接固定在骨上。水凝胶一直被认为是软组织替代的非常有前途的材料，可能为骨科植入物开辟新的市场。它们的采用受到机械性能差和断裂韧性低的阻碍。实验室测试表明，Orthonika的PVA-PEG材料具有卓越的机械和摩擦学性能，与天然组织的性能非常接近，并且上级目前用于其他应用的标准交联PVA水凝胶。在先前工作的基础上，Orthonika现在必须解决产品开发中的技术挑战，以证明临床规模生产的GMP可制造性以及随后在绵羊研究中的验证，针对首次人体临床研究项目后准备就绪。该项目使Orthonika能够：* 临床规模生产，桥接临床后验证的商业生产开发，以及 * 在绵羊研究中验证TMR植入物，从而加速转化为人类。这代表着商业化/临床应用的重大进展：* 为患者提供新的手术选择（膀胱切除术/TKR的替代方案）* 增强的医疗保健能力（与等待时间和患者恢复等关键绩效指标保持一致）* 服务于超过10亿英镑的全球市场 * 可能适应其他负载-轴承矫形应用（软骨、椎间盘）。

Over 4m people annually in the UK are affected by pain and immobility caused by a deficient meniscus, costing the equivalent of 1% GNP (NHS Business Plan 2017). The problem goes beyond age-related degenerative diseases and includes accidents/sports injuries in patients of any age.Technological challenges in developing load-bearing materials with suitable surface characteristics for such soft-tissue orthopaedic applications restrict options for treatment. In the absence of replacement devices, the standard of care for an irreparable meniscus is partial or complete removal (meniscectomy), with 2million/year such procedures world-wide (Li 2020).In response Orthonika, an SME spin-out from Imperial College London, has developed novel, reinforced load bearing PVA-PEG hydrogel materials for use in meniscus replacement. These unique materials are incorporated into an implant fixed directly to the bone via a reliable and established method.Hydrogels have long been thought of as highly promising materials for soft tissue replacements, potentially opening up new markets for orthopaedic implants. Their adoption has been hampered by poor mechanical properties and low fracture toughness. Laboratory tests have shown that Orthonika's PVA-PEG materials have exceptional mechanical and tribological properties that closely mimic those of natural tissue and are superior to the standard crosslinked PVA hydrogels currently in use for other applications.Building on previous work, Orthonika must now address technical challenges in product development to demonstrate GMP manufacturability for clinical-scale production and subsequent validation in ovine studies, targeting readiness for first-in-human clinical studies post-project.The project enables Orthonika to:* Manufacture at clinical-scale, bridging to development for commercial manufacturing post-clinical validation and* Validate the TMR implant in ovine studies and therefore accelerate translation to human.This represents significant progression towards commercialisation/clinical uptake:* New surgical options for patients (alternatives to meniscectomy/TKR)* Enhanced healthcare capabilities (alignment with key performance indicators such as wait times and patient recovery)* Servicing a £1bn+ global market* Potential adaptation to target other load-bearing orthopaedic applications (cartilage, intervertebral discs).