3D printing multifunctional devices without internal interfaces for cartilage repair

3D打印无内部接口的多功能软骨修复装置

• 批准号: EP/W034093/1
• 负责人: Julian Jones
• 金额: $ 78.41万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FW034093%2F1
• 关键词: 3D; printing; multifunctional; devices; without

We aim to create the first "inks" that can be used in additive manufacturing (vat based stereolithography) to produce complex architectures with stiffness and compositions gradients without any joins or internal interfaces. While this technology will have a wide range of applications, we will first use it to fulfil an unmet clinical need in orthopaedic surgery: devices that can heal damaged cartilage. Currently, there are very few, if any, materials that exist that have a true continuous composition or stiffness gradients. There are certainly none that have good mechanical properties. Sol-gel hybrid materials are assembled of intimately mixed co-networks of organic and inorganic components, but above the nanoscale they appear as single materials, distinguishing them from composite materials. Importantly, we have shown in our pilot studies that we can layer sol-gel materials as viscous liquids, just before they gel, so forming single materials with no internal joins or interfaces. We have 3D printed them, but only as grid-like architectures. Here, we will develop new hybrid inks that can be used to make complex pore architectures in vat based stereolithography (SLA), for the first time.Damage to articular cartilage due to sports injuries, trauma or age-related wear are increasingly likely as an active population ages. Current best practice for regeneration of small defects in knee cartialge is microfracture, which involves making small holes into the underlying bone to liberate the marrow, which fills the defect with weak fibrous cartilage. The cartilage only lasts 2-5 years before the procedure must be repeated. Eventually, total joint replacements are needed, which are major operations that involve removing a lot of tissue, and only last 15-25 years. Alternative medical devices are needed, e.g. using advanced materials with specifically designed chemistry and architecture. If successful, we can then apply the technology to help combat arthritis, something that effects everyone as they age. Our current 3D printed hybrid material shows great potential for regenerating cartilage because it provokes stem cells to produce articular cartilage-like matrix, rather than functionally inferior fibrocartilage. Importantly its mechanical properties can match that of the cartilage and transfer mechanical cues to the cells growing within it, which is critical for generation of high-quality cartilage. However, our previous 3D printing technique could only produce log-pile structures. The architecture of the device needs to be more complex. As cartilage is thin, most defects penetrate deep into the underlying bone, so we have designed a device that we hypothesise can regenerate the bone and the cartilage in appropriate locations. The part that goes into the bone will also be important for ensuring the implant stays in place during healing. Novelty of the research includes: the architectural design of the implant; the materials used to make it (new sol-gel hybrids that can be used in SLA) and the fact that sol-gel hybrids will be 3D printed in complex architectures (using SLA) for the first time. Following cell studies to show appropriate stimulus is provided to stem cells to send them down the required route (bone or cartilage), and ensuring potential for vascularized bone ingrowth, preclinical studies will be carried out. Our project partners will assist in technology transfer: Evonik and Makevale will produce the polymeric raw materials and Smith and Nephew will assess market potential, identify translation milestones and test our optimised device in their arthritis sheep model.This proposal will benefit medical device companies, patients, orthopaedic surgeons, and health services (e.g. the NHS) in a 10-20 year timeframe. As a third of workers are now over 50, it is critical that health services have access to technology that can allow patients to return to work quickly and reduce numbers of revision surgery.

我们的目标是创造第一种可用于增材制造（基于桶的立体光刻）的“墨水”，以生产具有刚度和成分梯度的复杂结构，而无需任何连接或内部界面。虽然这项技术将具有广泛的应用，但我们将首先使用它来满足骨科手术中未满足的临床需求：可以治愈受损软骨的设备。目前，具有真正连续成分或刚度梯度的材料（如果有的话）非常少。当然没有一种具有良好的机械性能。溶胶-凝胶杂化材料由有机和无机成分的紧密混合的共网络组装而成，但在纳米尺度以上，它们显示为单一材料，这与复合材料不同。重要的是，我们在试点研究中表明，我们可以在溶胶-凝胶材料凝胶之前将其分层为粘性液体，从而形成没有内部连接或界面的单一材料。我们已经 3D 打印了它们，但只是作为网格状架构。在这里，我们将首次开发新的混合墨水，可用于在基于缸的立体光刻 (SLA) 中制造复杂的孔隙结构。由于运动损伤、创伤或与年龄相关的磨损而导致的关节软骨损伤越来越有可能发生。活跃人口老龄化。目前膝关节软骨小缺损再生的最佳做法是微骨折，涉及在下面的骨头上打小孔以释放骨髓，从而用薄弱的纤维软骨填充缺损。软骨只能维持 2-5 年，之后必须重复手术。最终，需要进行全关节置换术，这是一项需要切除大量组织的重大手术，而且只能持续 15-25 年。需要替代的医疗设备，例如使用具有专门设计的化学和结构的先进材料。如果成功，我们就可以应用该技术来帮助对抗关节炎，关节炎是每个人随着年龄增长都会受到影响的疾病。我们目前的 3D 打印混合材料显示出软骨再生的巨大潜力，因为它能激发干细胞产生关节软骨样基质，而不是功能较差的纤维软骨。重要的是，它的机械性能可以与软骨相匹配，并将机械信号传递给其中生长的细胞，这对于生成高质量软骨至关重要。然而，我们之前的3D打印技术只能生产原木桩结构。设备的架构需要更加复杂。由于软骨很薄，大多数缺陷会深入到下面的骨骼中，因此我们设计了一种设备，我们假设可以在适当的位置再生骨骼和软骨。进入骨头的部分对于确保植入物在愈合过程中保持在适当的位置也很重要。研究的新颖性包括：植入物的结构设计；用于制造它的材料（可用于 SLA 的新型溶胶-凝胶混合物）以及溶胶-凝胶混合物将首次在复杂的架构中进行 3D 打印（使用 SLA）。细胞研究显示向干细胞提供了适当的刺激，使其沿着所需的路线（骨或软骨）发送，并确保血管化骨向内生长的潜力，随后将进行临床前研究。我们的项目合作伙伴将协助技术转让：赢创和Makevale将生产聚合物原材料，Smith and Nephew将评估市场潜力，确定转化里程碑并在关节炎羊模型中测试我们优化的设备。该提案将使医疗器械公司、患者受益、整形外科医生和卫生服务（例如 NHS）在 10-20 年的时间内。目前三分之一的工人已超过 50 岁，因此卫生服务部门必须能够获得能够让患者快速重返工作岗位并减少翻修手术数量的技术。