Material Design for Minimally Invasive Spinal Implant for Metastatic Bone Disease

这一博士学位是EPSRC项目Grant，OncoEng项目(www.oncoeng.org)的一部分，该项目旨在开发一种微创植入物(MII)，旨在支持脊椎负荷并防止受转移性骨病(MBD)影响的人发生骨折。这项博士研究的主要重点是设计和优化创建信息产业链的材料。多发性骨髓瘤是一种常见的癌症并发症，其发病率在多发性骨髓瘤中高达70-95%，在前列腺癌中高达65-90%，在乳腺癌中约为65-75%。多发性肌萎缩侧索硬化症主要发生在椎骨，导致神经压迫症状，严重时可导致截瘫。这种情况会对患者产生重大影响，包括疼痛、负重能力下降、日常活动受限和总体上，大大恶化患者的生活质量(QOL)。NHS癌症长期计划承认了绝症患者独特和个性化的需求，并强调了关于改善他们的生活质量的新干预措施的重要性。因此，需要开发一种能够填补脊柱转移瘤切除后留下的空白的植入物。MII的靶向轮廓需要它能够通过微创技术插入脊柱，并与周围骨的结构无缝匹配。作为回应，研究转向开发一种生物相容的、不透射线的材料，该材料具有维持脊柱脊椎负荷所需的机械性能。超材料被认为是适合于这一目的的材料，其特点是具有非自然或不寻常的性质，其规模小于块状现象。超材料的力学性能的提高源于在结构层次中组织的微尺度构建块的结合。因此，材料设计的挑战在于实现复杂的几何结构，其特征尺寸约为1um，这对获得所需的均质性和突现特性至关重要。在没有显著几何约束的情况下，不存在能够在3D中产生这样的特征分辨率的减法或成形制造。因此，人们探索了添加剂制造方法，其中VAT光聚合技术展示了高效生产复杂晶格的前景，这是MII开发不可或缺的一部分。VAT光聚合是一种3D打印过程，涉及通过光激活聚合选择性固化大量光固化材料。与其他3D打印技术相比，它具有最高的精度和分辨率。有多种热固性光聚合物可供选择，由于其表面光滑、多种多样的改性以及对当前灭菌方案的可行性，因此非常适合于医疗应用。研究小组成员之前的工作导致了用于制造候选材料的10种基础配方的开发。本论文的重点将是检查和优化这些配方，以达到MII开发所需的目标分辨率和物理性能。将采用VAT光聚合技术将材料打印成所需的复杂几何结构。

This PhD is part of the EPSRC Programme Grant, OncoEng project (www.oncoeng.org), which aims to develop a minimally invasive implant (MII) designed to support the vertebrae load and prevent fractures in people affected from metastatic bone disease (MBD). The primary focus of this PhD research involves the design and optimisation of the material for the creation of the MII. MBD denotes the infiltration of cancerous cells from primary tumours to the bone, and is a common complication of cancer with incidences reaching 70-95% in multiple myeloma, 65-90% in prostate cancer and approximately 65-75% in breast cancer. MBD occurs predominantly in the vertebrae and results in neurological compression symptoms, and in severe cases paraplegia. This condition can have a significant impact on patients, including pain, reduced weight-bearing capacity, limitations in daily activities and overall, substantially deteriorating the patient Quality of Life (QoL). Acknowledging the distinctive and personalized needs of terminally ill patients, the NHS Long Term Plan for Cancer hasemphasized the importance of new interventions regarding the improvement of their QoL. Consequently, there is a demand for the development of an implant capable of filling the void left by the removal of metastatic spinal lesions.The target profile of the MII entails its ability to be inserted into the spine with minimally invasive techniques, and seamlessly match the structure of the surrounding bone. In response, research has shifted towards developing a biocompatible, radiopaque material exhibiting the required mechanical properties to sustain the vertebral loads of the spine. Metamaterials, distinguished by non-natural or uncommon properties at a scale smaller than bulk phenomena, are deemed suitable for this purpose. The enhanced mechanical properties of metamaterials arise from the incorporation of micro-scale building blocks organized in a structured hierarchy. Thus, the challenge of the material design lies in achieving a complex geometric structure with a feature size on the order of 1 um, crucial for obtaining the desired homogeneity and emergent properties. No subtractive or forming manufacturing exists that can produce such feature resolution in 3D without significant geometric constraints. Consequently, additive manufacturing methods have been explored, with VAT photopolymerizationtechniques demonstrating promise in efficiently producing intricate lattices integral to the MII development.VAT photopolymerization is a 3D printing process which involves selectively curing a volume of photocurable material through light-activated polymerization. It has been shown to have the highest accuracy and resolution compared to other 3D printing technologies. A wide range of thermosetting photopolymers are available which are well suited to medical applications due to their smooth surface finish, versatile modification and viability for current sterilization protocols. Previous work by members of the research group has led to the development of 10 base formulations for the fabrication of the candidate material. The focus of this thesis will be to examine and optimise these formulations to achieve the target resolution and physical properties required for the development of the MII. VAT photopolymerization will be employed to print the material into the intricate geometrical structures required.