Material Design for Minimally Invasive Spinal Implant for Metastatic Bone Disease

该博士学位是EPSRC计划资助，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），旨在支持椎骨负荷并防止受转移性骨病（MBD）影响的人骨折。该博士研究的主要重点涉及MII创建材料的设计和优化。MBD表示癌细胞从原发性肿瘤浸润到骨，并且是癌症的常见并发症，在多发性骨髓瘤中的发病率达到70-95%，在前列腺癌中的发病率达到65-90%，在乳腺癌中的发病率达到约65-75%。MBD主要发生在椎骨中，并导致神经压迫症状，在严重的情况下导致截瘫。这种情况可能对患者产生显著影响，包括疼痛、承重能力降低、日常活动受限以及总体上显著降低患者生活质量（QoL）。认识到绝症患者的独特和个性化的需求，NHS癌症长期计划强调了改善其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充转移性脊柱病变切除后留下的空隙的植入物。MII的目标轮廓要求其能够通过微创技术插入脊柱中，并与周围骨的结构无缝匹配。作为回应，研究已经转向开发具有生物相容性、不透射线的材料，该材料表现出维持脊柱的椎骨负荷所需的机械性能。超材料，以非自然或不寻常的性质在比块现象小的尺度上区分，被认为适合于此目的。超材料的增强的机械性能来自于在结构化层次结构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具有1 μ m量级特征尺寸的复杂几何结构，这对于获得所需的均匀性和涌现特性至关重要。不存在可以在没有显著几何约束的情况下在3D中产生这样的特征分辨率的减材制造或成形制造。因此，已经探索了增材制造方法，其中VAT光聚合技术在有效生产MII开发中不可或缺的复杂晶格方面表现出希望。VAT光聚合是一种3D打印工艺，其涉及通过光活化聚合选择性地固化一定体积的光固化材料。与其他3D打印技术相比，它具有最高的精度和分辨率。有各种各样的热固性光聚合物可供选择，由于其光滑的表面光洁度，多功能的改性和当前灭菌方案的可行性，这些光聚合物非常适合医疗应用。该研究小组成员先前的工作已经导致开发了用于制造候选材料的10种基础配方。本论文的重点将是检查和优化这些配方，以达到目标的分辨率和所需的MII的发展物理性能。VAT光聚合将用于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.