Rapid Design of Bioinspired Alloys - From Modelling to Manufacture

仿生合金的快速设计 - 从建模到制造

• 批准号: MR/T017783/1
• 负责人: Sophie Cox
• 金额: $ 155.84万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT017783%2F1
• 关键词: Rapid; Design; Bioinspired; Alloys; Modelling

In the past decade, over 2.5 million people in the UK had a metal device implanted to replace a skeletal joint in their body. With our chances of living to 100 years old predicted to double in the next 50 years, these bone implants will need to last substantially longer. Alarmingly, current data demonstrates that failure rates rapidly increase each subsequent year after implantation. The metals we currently make bone implants from were not specifically developed for use within the body. Instead, these materials were originally designed for aerospace applications. In addition to being much stiffer than bone, these metal alloys may also contain toxic elements that cause adverse biological reactions. The aim of this fellowship is to design a new generation of bioinspired alloys that promote advantageous cellular responses while exhibiting mechanical properties that are aligned with the body. In order to design the ideal biomedical alloy, there are a number of properties that need to be balanced, for example biocompatibility (i.e. non-toxic), mechanical performance, and wear resistance. Optimising lots of parameters simultaneously via current trial-and-error approaches may take years or even decades. To significantly speed up this process, a computational modelling approach, called Alloys-By-Design (ABD), will be used to discover a range of titanium compositions that match the mechanical properties of bone. For the first time, by searching for alloys with specific microstructures, ABD will be employed to identify compositions with promising biological functionality, such as infection prevention. Since ABD is a theory-based approach, it will be important to validate the model predictions. This will be done by using a unique laser-based system to melt together all the alloying elements. To maintain rapid progress towards using these new metals clinically, a novel high throughput test will be developed as a screening tool to identify compositions that provoke promising mammalian and bacterial cell responses. From these results, non-toxic and antimicrobial compositions will be selected. High resolution microscopy will subsequently be used to understand the relationships between alloying elements, microstructure and biological behaviour. Before bone implants made of these new alloys may be implanted into patients, it will be critical to deepen our understanding of how the body may respond. Importantly, the behaviour of various cell types involved in bone regeneration will be considered, including bone forming osteoblasts and stem cells found in bone marrow. The rate at which these cells grow and their ability to form new bone on the surface of the novel alloys will be benchmarked against currently used metals. Since it is known that ions may leach from alloys within the body and cause damage to surrounding tissue, this will also be carefully studied. The patient and economic benefits gained from personalised devices that anatomically fit perfectly is rapidly growing in bone implants. As such, the possibility to 3D print bespoke implants made from the most promising bioinspired alloy will be explored. For the first time, the ability to locally tailor alloy composition in-situ using a metal laser-based 3D printer will be investigated. By systematically changing the laser processing parameters and characterising the resultant composition, a universal protocol to optimise in-situ alloy formation will be developed. This will open up an entirely new dimension of bone implant customisation, making it possible to tailor mechanical performance or biological functionality in selected areas of a single implant. Underpinning this fellowship is an experienced clinical and industrial advisory board that will support translation of these novel bioinspired alloys. This will ensure that the research may be transformed into approved medical devices that improve patient lives, reduce healthcare costs, and grow the UK economy.

在过去的十年中，英国有超过250万人植入了金属装置来取代他们体内的骨骼关节。随着我们活到100岁的机会预计在未来50年内翻一番，这些骨植入物将需要持续更长时间。令人担忧的是，目前的数据表明，植入后每年的失败率迅速增加。我们目前制造骨植入物的金属并不是专门为体内使用而开发的。相反，这些材料最初是为航空航天应用而设计的。除了比骨头硬得多之外，这些金属合金还可能含有引起不良生物反应的有毒元素。该奖学金的目的是设计新一代生物启发合金，促进有利的细胞反应，同时表现出与身体一致的机械性能。为了设计理想的生物医学合金，需要平衡许多特性，例如生物相容性（即无毒），机械性能和耐磨性。通过目前的试错法同时优化许多参数可能需要几年甚至几十年的时间。为了显著加快这一过程，将使用一种名为Alloys-By-Design（ABD）的计算建模方法来发现一系列与骨骼机械性能相匹配的钛成分。通过寻找具有特定微观结构的合金，ABD将首次用于识别具有有希望的生物功能的组合物，例如预防感染。由于ABD是一种基于理论的方法，因此验证模型预测非常重要。这将通过使用独特的基于激光的系统将所有合金元素熔化在一起来完成。为了保持在临床上使用这些新金属的快速进展，将开发一种新的高通量测试作为筛选工具，以鉴定引起有希望的哺乳动物和细菌细胞反应的组合物。从这些结果中，将选择无毒和抗微生物的组合物。高分辨率显微镜随后将用于了解合金元素，微观结构和生物行为之间的关系。在将这些新合金制成的骨植入物植入患者体内之前，加深我们对身体如何反应的理解至关重要。重要的是，将考虑参与骨再生的各种细胞类型的行为，包括骨髓中发现的成骨细胞和干细胞。这些细胞生长的速度和它们在新型合金表面形成新骨的能力将以目前使用的金属为基准。由于已知离子可能从体内的合金中浸出并对周围组织造成损伤，因此也将对其进行仔细研究。从解剖学上完美匹配的个性化器械中获得的患者和经济效益在骨植入物中迅速增长。因此，将探索由最有前途的生物启发合金制成的3D打印定制植入物的可能性。将首次研究使用金属激光3D打印机原位定制合金成分的能力。通过系统地改变激光加工参数和表征所得的组合物，将开发一种通用的协议，以优化原位合金形成。这将为骨植入物定制开辟一个全新的维度，使其能够在单个植入物的选定区域定制机械性能或生物功能。该奖学金的基础是一个经验丰富的临床和工业咨询委员会，将支持这些新型生物启发合金的翻译。这将确保该研究可以转化为经批准的医疗设备，改善患者生活，降低医疗成本，并促进英国经济增长。

项目成果

Stakeholder Perspectives on the Current and Future of Additive Manufacturing in Healthcare.

• DOI: 10.18063/ijb.v8i3.586
• 发表时间: 2022
• 期刊: INTERNATIONAL JOURNAL OF BIOPRINTING
• 影响因子: 8.4
• 作者: Villapun, Victor M.;Carter, Luke N.;Avery, Steven;Gonzalez-Alvarez, Alba;Andrews, James W.;Cox, Sophie
• 通讯作者: Cox, Sophie

Exploring the duality of powder adhesion and underlying surface roughness in laser powder bed fusion processed Ti-6Al-4V

• DOI: 10.1016/j.jmapro.2022.06.057
• 发表时间: 2022-09-01
• 期刊: JOURNAL OF MANUFACTURING PROCESSES
• 影响因子: 6.2
• 作者: Carter, Luke N.;Villapun, Victor M.;Cox, Sophie C.
• 通讯作者: Cox, Sophie C.

Surface Free Energy Dominates the Biological Interactions of Postprocessed Additively Manufactured Ti-6Al-4V.

• DOI: 10.1021/acsbiomaterials.2c00298
• 发表时间: 2022-10-10
• 期刊: ACS BIOMATERIALS SCIENCE & ENGINEERING
• 影响因子: 5.8
• 作者: Puzas, Victor Manuel Villapun;Carter, Luke N.;Schroder, Christian;Colavita, Paula E.;Hoey, David A.;Webber, Mark A.;Addison, Owen;Shepherd, Duncan E. T.;Attallah, Moataz M.;Grover, Liam M.;Cox, Sophie C.
• 通讯作者: Cox, Sophie C.

Development of a Bone-Mimetic 3D Printed Ti6Al4V Scaffold to Enhance Osteoblast-Derived Extracellular Vesicles' Therapeutic Efficacy for Bone Regeneration.

• DOI: 10.3389/fbioe.2021.757220
• 发表时间: 2021
• 期刊: Frontiers in bioengineering and biotechnology
• 影响因子: 5.7
• 作者: Man K;Brunet MY;Louth S;Robinson TE;Fernandez-Rhodes M;Williams S;Federici AS;Davies OG;Hoey DA;Cox SC
• 通讯作者: Cox SC