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导致的疼痛和行动不便的影响，损失相当于1%的国民生产总值(NHS商业计划2017)。问题不仅仅是与年龄相关的退行性疾病，还包括任何年龄患者的意外/运动损伤。为此类软组织矫形应用开发具有合适表面特征的承重材料的技术挑战限制了治疗选择。在缺乏替代装置的情况下，对不可修复的半月板的护理标准是部分或完全切除(半月板切除)，全球每年有200万例这样的手术(Li 2020)。对此，从伦敦帝国理工学院剥离出来的中小型企业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一种可靠和成熟的方法被结合到直接固定在骨骼上的植入物中。长期以来，水凝胶一直被认为是非常有前途的软组织替代材料，可能会为骨科植入物打开新的市场。由于机械性能差和断裂韧性低，它们的采用受到了阻碍。实验室测试表明，Orthonika的PVA-PEG材料具有非常出色的机械和摩擦学特性，非常接近自然组织的那些特性，并且优于目前用于其他应用的标准交联PVA水凝胶。在以前工作的基础上，Orthonika现在必须解决产品开发中的技术挑战，以证明GMP可用于临床规模生产和随后的绵羊研究验证，目标是为项目后的第一次人类临床研究做好准备。该项目使Orthonika能够：*临床规模的制造，为商业生产搭建桥梁--临床后验证和*在绵羊研究中验证TMR植入物，从而加快向人类的转化。这代表着朝着商业化/临床应用的重大进展：*患者的新手术选择(半月板切除/TKR的替代方案)*增强的医疗能力(与等待时间和患者恢复等关键性能指标保持一致)*服务于10亿GB+全球市场*针对其他承重矫形应用(软骨、椎间盘)的潜在适应。

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).