Novel Models for Haemodynamics and Transport in Complex Media: Towards Precision Healthcare for Placental Disorders

复杂介质中血流动力学和运输的新模型：迈向胎盘疾病的精准医疗保健

• 批准号: EP/T008725/1
• 负责人: Igor Chernyavsky
• 金额: $ 92.11万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FT008725%2F1
• 关键词: Novel; Models; Haemodynamics; Transport; Complex

Pre-term and stillbirths affect up to 10% of all deliveries, including in developed countries, such as the UK. Among these complications, pre-eclampsia, or the compromised supply of blood between mother and fetus via the placenta, costs over £1.2 billion each year in neonatal and infant care to the NHS and public sector services in the UK alone.The human placenta is a vital life-support system for the developing fetus. The supply of oxygen and nutrients by the mother's blood has to be well orchestrated within a complex fetal blood vessel network. There are two reasons for our limited progress in the understanding of the interaction of the structure and the function of the placenta: on the one hand, the human placenta has an extraordinarily complex structure; on the other hand, the structure and physiology of the human placenta are unique and therefore animal studies are of limited use. A direct consequence of the lack of understanding are very limited options for clinical management of pregnancy diseases such as pre-eclampsia and fetal growth restriction. Furthermore, placental insufficiency does not only result in stillbirth or premature delivery, but it has also been associated with a higher risk of heart attack, stroke, diabetes or neurological disorders later in adult life.Recognition of these challenges has resulted in a recent surge of research interest world-wide and in establishing the $41M US Human Placenta Project and the EU Placentology Network for experimental and theoretical testing of chemicals' safety in pregnancy. Moreover, a recent breakthrough in 'artificial placenta' design for life-support of extremely premature infants offers new opportunities for design optimisation by systematic 'reverse engineering' of the normal human placenta. Thus, the UK needs a critical mass of expertise in placental technologies to match the US and EU capacities and to remain an active player in international collaborations in this important area.Based on our research to date, we hypothesise that blood flow and nutrient transport in the placenta are altered in pre-eclampsia and fetal growth restriction. In this project, we propose an interdisciplinary and innovative approach harnessing our theoretical and experimental expertise to deliver precision medicine for obstetrics and neonatal critical care. We will develop and validate a framework for image-based modelling and simulation of blood flow and nutrient transport in patient-specific placentas. Thanks to existing datasets describing the structure of both healthy and diseased placentas, we will be able to explore which anatomical changes in the placenta are associated with compromised nutrient transport. This will establish a sound theoretical basis for the development of interventions and artificial solutions for the treatment of pre-eclampsia and fetal growth restriction. The long-term translational impacts include (i) model-based patient-specific treatment with drugs avoiding placental dysfunction in high-risk pregnancies and (ii) design optimisation of an 'artificial placenta' for the support of extremely premature babies.

早产和死产对所有分娩的影响高达10%，包括在英国等发达国家。在这些并发症中，先兆子痫，即母亲和胎儿之间通过胎盘的血液供应受损，仅在英国就为NHS和公共部门服务的新生儿和婴儿护理每年花费超过12亿GB。人类胎盘是发育中的胎儿至关重要的生命维持系统。母亲血液中的氧气和营养物质的供应必须在一个复杂的胎儿血管网络中得到很好的协调。我们在了解胎盘结构和功能的相互作用方面进展有限的原因有两个：一方面，人类胎盘具有极其复杂的结构；另一方面，人类胎盘的结构和生理是独一无二的，因此动物研究的作用有限。缺乏了解的一个直接后果是临床治疗妊娠疾病的选择非常有限，如先兆子痫和胎儿生长受限。此外，胎盘不足不仅会导致死产或早产，还会增加成年后心脏病发作、中风、糖尿病或神经系统疾病的风险。认识到这些挑战，最近在全球范围内引起了研究兴趣的激增，并建立了耗资4100万美元的美国人类胎盘项目和欧盟胎盘学网络，用于对怀孕期间化学物质的安全性进行实验和理论测试。此外，最近在为极早产儿提供生命支持的“人造胎盘”设计方面的突破，为通过对正常人类胎盘进行系统化的“逆向工程”来优化设计提供了新的机会。因此，英国需要大量胎盘技术方面的专业知识，以匹配美国和欧盟的能力，并在这一重要领域的国际合作中保持积极的参与者。基于我们迄今的研究，我们假设胎盘中的血流和营养物质运输在先兆子痫和胎儿生长受限中发生了改变。在这个项目中，我们提出了一种跨学科的创新方法，利用我们的理论和实验专业知识为产科和新生儿危重护理提供精确的医学。我们将开发和验证一个框架，用于基于图像的建模和模拟患者特定胎盘中的血液流动和营养运输。由于现有的数据集描述了健康和患病胎盘的结构，我们将能够探索胎盘中的哪些解剖变化与营养物质运输受损有关。这将为开发治疗子痫前期和胎儿生长受限的干预措施和人工解决方案奠定坚实的理论基础。长期的翻译影响包括(I)基于模型的针对患者的治疗，使用药物避免高危妊娠中的胎盘功能障碍，以及(Ii)优化“人造胎盘”的设计，以支持极早产儿。

项目成果

Self-assembly of coated microdroplets at the sudden expansion of a microchannel

• DOI: 10.1007/s10404-021-02424-z
• 发表时间: 2021-03-01
• 期刊: MICROFLUIDICS AND NANOFLUIDICS
• 影响因子: 2.8
• 作者: Schirrmann, Kerstin;Caceres-Aravena, Gabriel;Juel, Anne
• 通讯作者: Juel, Anne

Robust fabrication of ultra-soft tunable PDMS microcapsules as a biomimetic model for red blood cells.

稳健地制造超软可调 PDMS 微胶囊作为红细胞的仿生模型。

• DOI: 10.1039/d3sm00208j
• 发表时间: 2023
• 期刊: Soft matter
• 影响因子: 3.4
• 作者: Chen Q

Advection-dominated transport past isolated disordered sinks: stepping beyond homogenization.

• DOI: 10.1098/rspa.2022.0032
• 发表时间: 2022-06
• 期刊: PROCEEDINGS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
• 影响因子: 3.5
• 作者: Price, George F.;Chernyavsky, Igor L.;Jensen, Oliver E.
• 通讯作者: Jensen, Oliver E.

Supplementary Material from Red blood cell dynamics in extravascular biological tissues modelled as canonical disordered porous media

血管外生物组织中红细胞动力学的补充材料，模型为典型的无序多孔介质

• DOI: 10.6084/m9.figshare.21117053
• 发表时间: 2022
• 作者: Zhou Q

Supplementary Methods and Results from A massively multi-scale approach to characterizing tissue architecture by synchrotron micro-CT applied to the human placenta

通过同步加速器微型 CT 应用于人类胎盘来表征组织结构的大规模多尺度方法的补充方法和结果

• DOI: 10.6084/m9.figshare.14615128
• 发表时间: 2021
• 作者: Tun W