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个可用于加法制造(基于VAT的立体平版印刷)的“油墨”，以生产具有刚性和组成梯度的复杂结构，而不需要任何连接或内部界面。虽然这项技术将有广泛的应用，但我们将首先使用它来满足矫形外科中一个尚未满足的临床需求：可以修复受损软骨的设备。目前，很少(如果有)材质具有真正的连续合成或刚度渐变。当然，没有一种具有良好的机械性能。溶胶-凝胶杂化材料是由有机和无机组分紧密混合的共聚网络组装而成，但在纳米级以上，它们看起来像是单一材料，与复合材料不同。重要的是，我们已经在我们的初步研究中表明，我们可以在溶胶-凝胶材料凝胶化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。我们已经用3D打印了它们，但只是作为网格状的建筑。在这里，我们将开发新的混合油墨，可用于在基于VAT的立体光刻术(SLA)中制造复杂的孔结构。随着活跃人口的老龄化，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的可能性越来越大。目前修复膝盖骨小缺损的最佳方法是微骨折，即在下面的骨中打小孔以释放骨髓，从而用脆弱的纤维软骨填充缺损处。在必须重复这一过程之前，软骨只能持续2-5年。最终，需要进行全关节置换，这是一种需要移除大量组织的大手术，而且只能持续15-25年。需要替代医疗设备，例如使用具有专门设计的化学和建筑的先进材料。如果成功，我们就可以应用这项技术来帮助抗击关节炎，这种疾病会随着年龄的增长而影响每个人。我们目前的3D打印混合材料显示出巨大的软骨再生潜力，因为它能刺激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生长在其中的细胞，这对生成高质量的软骨至关重要。然而，我们之前的3D打印技术只能产生原木堆结构。该设备的架构需要更复杂。由于软骨很薄，大多数缺陷会深入到下面的骨中，所以我们设计了一种装置，我们假设可以在适当的位置再生骨和软骨。进入骨骼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是重要的。这项研究的新颖性包括：植入物的建筑设计；用于制造植入物的材料(可用于SLA的新型溶胶-凝胶杂化材料)，以及将首次在复杂的建筑中进行3D打印的事实(使用SLA)。在细胞研究表明向干细胞提供适当的刺激以将它们送往所需的途径(骨或软骨)并确保血管化骨向内生长后，将进行临床前研究。我们的项目合作伙伴将协助技术转让：Evonik和Makevale将生产聚合物原材料，Smith和Nephew将评估市场潜力，确定翻译里程碑，并在他们的关节炎绵羊模型中测试我们优化的设备。这项提议将在10-20年内使医疗器械公司、患者、矫形外科医生和健康服务机构(如NHS)受益。由于三分之一的工人现在超过50岁，卫生服务机构能够获得能够让患者迅速重返工作岗位并减少翻修手术数量的技术是至关重要的。