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Details of Grant 

EPSRC Reference: EP/T023155/1
Title: A platform for studying the role of haemodynamics in microvascular disease
Principal Investigator: Sherwood, Dr JM
Other Investigators:
Researcher Co-Investigators:
Project Partners:
University of Delaware
Department: Bioengineering
Organisation: Imperial College London
Scheme: New Investigator Award
Starts: 11 January 2021 Ends: 10 January 2023 Value (£): 313,245
EPSRC Research Topic Classifications:
Complex fluids & soft solids Rheology
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
05 Aug 2020 Engineering Prioritisation Panel Meeting 5 and 6 August 2020 Announced
Summary on Grant Application Form
In order to function, all cells in the body require a regular supply of oxygen and continuous removal of waste products. Both are provided by blood delivered through the microvasculature, which comprises vessels smaller than 0.1 mm in diameter. In order to fulfil its function, the flow of blood must be tightly regulated. A key component of this regulation are the specialist 'endothelial cells' that line all microvessels. These cells sense frictional forces arising from the flowing blood and in response release chemical substances that can increase or decrease the size of the vessels to help regulate the flow. When this regulation fails, the results can be devastating. For example, dysregulation of blood flow is one of the first stages in diabetic retinopathy, a condition that threatens the sight of 1% of the world's adult population.

It is therefore important to understand the details of how blood flows in microvessels. A major factor that influences microvascular blood flow is the mechanical properties of red blood cells (RBCs). RBCs are highly deformable, which allows them to deform while flowing in larger vessels and even fit through capillaries much smaller than their diameter. RBCs also have a propensity to stick together, in a process called aggregation that is dependent on local flow characteristics. As a result of these RBC behaviours, the flow of blood in microvessels is complex and poorly understood. This is particularly important, because in numerous microvascular diseases, including diabetes, the RBCs become less deformable and aggregate more than in healthy individuals. These changes have been shown to correlate with disease progression, but it has not yet been established exactly how changes to blood properties affect microvascular function.

We hypothesise that the changes in RBC properties alter blood flow and hence the frictional forces experienced by the endothelial cells, which in turn leads to dysregulation of flow and ultimately damage to the microvasculature. In this project, we will use state-of-the-art experimental technology to directly evaluate how changes to RBC properties affect microscale blood flow.

A key challenge is the complicated branching patterns of the microvessel network. These networks consist of vessels of different sizes, structure and functions, throughout which both RBC flow and concentration change significantly. In order to improve our knowledge of how blood flows in microvessels, we need to be able to measure both the velocity of the RBCs and their local concentration in a given blood vessel or section of a microvascular network. We will achieve this using recently developed optical techniques, combining measurements of light passing through a blood sample with fluorescence measurements of microparticles added to the plasma. Acquiring both of these parameters allows calculation of the frictional forces on the vessel wall, which will be compared to results generated with numerical models.

It is not currently possible to make these measurements in humans or living animals, hence we will build realistic models of microvessels using a new technique where laser energy is used to degrade a hydrogel, leaving behind a vessel structure that can be precisely controlled. We will flow blood from healthy volunteers through these models and measure the flow and wall friction under various conditions. We will then chemically treat the blood samples to mimic changes that occur in diabetes and measure the corresponding changes in flow.

In addition to providing new insight into blood flow, the evidence generated in this study will reveal how changes to blood mechanical properties might affect diseases such as diabetes. In the long term, this insight is expected to lead to new approaches for diagnosing and treating microvascular diseases.

Key Findings
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Organisation Website: http://www.imperial.ac.uk