Design Optimisation of Tissue Scaffolds Using Patient-specific and In Vivo Criteria

使用患者特异性和体内标准优化组织支架的设计

• 批准号: EP/N006089/1
• 负责人: Yuhang Chen
• 金额: $ 12.71万
• 依托单位: Heriot-Watt University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FN006089%2F1
• 关键词: Design; Optimisation; Tissue; Scaffolds; Using

Background:As a result of increasing life expectancy diseases in bone and various types of soft tissue have become a major health concern. For example, in the UK, musculoskeletal conditions are a major area of NHS expenditure, consuming £4.76 billion in 2009-2010 alone. Currently cancer affects one in three of us during our lifetime and, in 2010, the costs of cancer diagnosis and treatment across the UK was estimated at £9.4 billion. The treatment process can require significant amounts of tissue to be removed or destroyed, with the resulting damage requiring a supply of appropriate viable tissues from the patient or from donors which may be of limited availability. Tissue engineering, as a fast emerging interdisciplinary area, offers enormous potential to solve such a critical problem in public health and socio-economy. Not only does the scaffold create a structural matrix to generate the required spatial tissue anatomy, but also provides a vehicle for the nutrient intake and waste product removal from/to the surrounding environment necessary for cell proliferation and tissue growth. However, there remain critical challenges, including a 'lack of quantitative design optimisation approach for scaffold architecture' and 'how to incorporate in vivo environment and patient-specific factors in scaffold selection', which to some extent prevent tissue engineering from being translated to a clinically-adoptable technology.Programme and MethodologyThis First Grant proposes to address the challenges identified above and, more importantly, to make critical steps forward in bridging the gap between the advances in in vitro tissue engineering and its ultimate goal of 'in vivo tissue regeneration' by giving it an additional dimension of vitality, i.e. design optimisation of scaffolds subject to tissue-specificity and patient-specificity. The approach taken here is to establish a design optimisation framework that considers different tissue environment, the underlying engineering challenges of scaffolding in vivo, and the fluid and solid mechanics problems involved, using state-of-the-art computational tools including structural optimisation and inverse homogenisation. This project aims to address the following critical aspects in the design process of scaffold microstructure: i) Permeability of scaffold microstructure will be optimised towards the degree of anisotropy in the local microfluidic environment near the scaffold-host interface; ii) To improve the transport capacity of large scaffolds, a gradient transport property across the scaffold will be obtained by applying a gradient test field (macroscopically uniform but microscopically gradient); iii) An additional optimisation objective with respect to the minimisation of interfacial stress will be introduced, which not only dictates that the scaffold geometrically fits into the tissue cavity but also ensures that the interfacial stress caused by the possible relative movement between scaffold and the host tissue can be kept to a minimum; iv) A multi-objective optimisation scheme that takes into account the microenvironment of host tissue affected by both tissue-specific and patient-specific factors; v) The effective capacity of oxygen diffusion and nutrient supply in the scaffold microstructure will then be evaluated by an in silico mass diffusion model. Project OutcomeThe ultimate deliverable from this First Grant is a novel design optimisation tool for tissue scaffold. This tool will, for the first time, enable the scaffold microstructures to be designed towards individual and personalised use in vivo. Clinical RelevanceThe project also benefits from a clinical advisor who can provide not only additional sustainability to the programme and bring a new collaboration and clinical contacts from the NHS, but also the biomedical context to ensure that the implications of any simplifications can be addressed in future work.

背景：由于预期寿命的增加，骨骼和各种软组织疾病已成为一个主要的健康问题。例如，在英国，肌肉骨骼疾病是NHS支出的一个主要领域，仅在2009-2010年就消耗了47.6亿英镑。目前，在我们的一生中，有三分之一的人受到癌症的影响。2010年，全英国癌症诊断和治疗的费用估计为94亿英镑。治疗过程可能需要移除或破坏大量组织，由此造成的损伤需要患者或供体提供适当的有活力的组织，而这些组织的可用性可能有限。组织工程作为一个新兴的跨学科领域，为解决公共卫生和社会经济中的关键问题提供了巨大的潜力。支架不仅创造了一个结构基质来产生所需的空间组织解剖结构，而且还为细胞增殖和组织生长所需的营养摄入和废物从周围环境中去除提供了载体。然而，仍然存在重大挑战，包括“缺乏支架结构的定量设计优化方法”和“如何在支架选择中纳入体内环境和患者特异性因素”，这在一定程度上阻碍了组织工程转化为临床可采用的技术。项目和方法第一笔拨款旨在解决上述挑战，更重要的是，通过赋予体外组织工程额外的活力维度，即根据组织特异性和患者特异性优化支架设计，在弥合体外组织工程进步与其“体内组织再生”最终目标之间的差距方面迈出关键一步。这里采取的方法是建立一个设计优化框架，考虑不同的组织环境，体内支架的潜在工程挑战，以及所涉及的流体和固体力学问题，使用最先进的计算工具，包括结构优化和逆均质化。本项目旨在解决支架微观结构设计过程中的以下关键问题：i)在支架-宿主界面附近的局部微流控环境中，支架微观结构的渗透率将朝着各向异性的程度进行优化；ii)为了提高大型支架的运输能力，将通过施加梯度试验场（宏观上均匀但微观上梯度）来获得支架的梯度运输特性；iii)将引入关于界面应力最小化的额外优化目标，这不仅规定了支架在几何上适合于组织腔，而且确保由支架和宿主组织之间可能的相对运动引起的界面应力可以保持在最小；iv)考虑到受组织特异性和患者特异性因素影响的宿主组织微环境的多目标优化方案；v)然后通过硅质扩散模型评估支架微观结构中氧气扩散和营养供应的有效能力。第一笔拨款的最终成果是一种新的组织支架设计优化工具。该工具将首次使支架微结构能够设计为个体和个性化的体内使用。临床相关性该项目还受益于临床顾问，他不仅可以为项目提供额外的可持续性，并带来来自NHS的新的合作和临床联系，而且还可以提供生物医学背景，以确保任何简化的影响都可以在未来的工作中得到解决。

项目成果

Locating and sizing tumor nodules in human prostate using instrumented probing - computational framework and experimental validation.

使用仪器探测-计算框架和实验验证来定位人类前列腺中的肿瘤结节并确定其大小。

• DOI: 10.1080/10255842.2022.2065200
• 发表时间: 2023
• 期刊: Computer methods in biomechanics and biomedical engineering
• 影响因子: 1.6
• 作者: Candito A

Computational homogenization of histological microstructures in human prostate tissue: Heterogeneity, anisotropy and tension-compression asymmetry

• DOI: 10.1002/cnm.3758
• 发表时间: 2023-07-21
• 期刊: INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING
• 影响因子: 2.1
• 作者: Anderson，Calum;Ntala，Chara;Chen，Yuhang
• 通讯作者: Chen，Yuhang