Aston University

"The innovations in chronic wound care have been inadequate, proving to be a significant challenge to treat successfully chronic wounds, due to their inability to heal quickly like acute wounds. Some chronic wounds never recover leading to sepsis or amputations. Patients with chronic wounds can require hospitalisation for long periods of time, which puts an increased strain on health care services. Chronic wounds are not completely understood, there are important steps that are carried out in sequence within the body to heal wounds, these are: homeostasis, inflammation, proliferation and remodelling but chronic wounds do not progress beyond the inflammation stage. Hydrogels It has become recognised that chronic wounds heal better when maintained in a moist environment. Hydrogels are three-dimensional hydrophilic networks that can be synthetically designed to absorb ca. 1000 times their weight of water without solubilising. When swollen they are able to simulate biological tissue. They possess the majority of the ideal characteristics required of dressings, in particular that of managing the wound bed moisture, a cooling effect believed to considerably reduced the pain associated with the wound, enable gaseous exchange and can be removed without causing further trauma. For these reasons they are used as dressings for dry, sloughy, or necrotic wounds. One disadvantage, however, is that when swollen they lose structural integrity. Interpenetrating network (IPN) hydrogels are hydrogels that contain two or more cross-linked polymeric units, which are structurally more favourable due to their increased strength and stability upon swelling. They are particularly interesting for biomedical use, as they share similarities with the extracellular matrix, due to cells containing many proteins, IPN can consist of many polymer units, these similarities make them an excellent candidate for wound dressings to aid in tissue regeneration. Project aim In this project we propose to design a dressing to stimulate extracellular matrix (ECM) synthesis to promote progress through the proliferation wound healing stage. The ECM is heterogeneous and in a healthy environment is constantly renewed. It consists of two main components glycoproteins (fibronectin, proteoglycans, laminin) and fibrous proteins (collagen, elastin). The ECM influences the differentiation as well as anchorage and attachment of connective tissue to enhance the healing process. The design of a wound dressing capable of regulating ECM activity is therefore a desirable objective. In this project, it is thus proposed that the design of hydrogel-based dressings consisting of polymeric networks with the potential to mimic the ECM are explored further. The use of synthetic materials will provide the ability to tune the hydrogel, to produce a stronger wound dressing, that enables gaseous exchange and absorption of excess wound exudate, without losing structural integrity and enabling the wound to heal and progress beyond the inflammatory stage. A cost-effective hydrogel will be developed that consists of an interpenetration network of crosslinked polymers, that provides adequate strength upon swelling. Appropriate monomer units, from natural or synthetic materials, will be selected to suit the healing of chronic wounds. The polymerisation process will be optimised, the properties of the hydrogel that will be assessed are equilibrium water content (EWC), mechanical and peel strength, viscoelastic properties and water vapour sorption properties. "

The rising burden of metabolic disease, including obesity and type 2 diabetes mellitus is a substantial concern for healthcare systems worldwide. In 2016 1.9 billion people were classed as overweight or obese and worldwide 1 in 11 people have the most common form of diabetes, type 2. Metabolic disease is associated with a wide array of nutrient homeostasis dysfunction, including insulin resistance, elevated blood glucose (in diabetes), dyslipidaemia and hepatic steatosis. These associated issues drive disease burden which has led to diabetes alone consuming around 10% of the entire NHS budget. Identifying therapeutic targets to correct this nutrient homeostasis dysfunction is therefore paramount to mitigate the impacts of both obesity and diabetes. The ATP-binding cassette transporters (ABC transporters) are a superfamily of integral membrane proteins, which use energy from ATP hydrolysis to transport substrates across the membrane. There are more than 250 members in the ABC superfamily that can be thought of as 'importers' or 'exporters'. Whilst importers only exist in prokaryotes, both eukaryotes and prokaryotes possess ABC transporters that function to export substrates out of the cytosol, either into an organelle, or out of the cell. Humans have 48 different ABC transporters, and several of these transport lipids, including ABCA1 which transports phospholipids and cholesterol, ABCD1 which transports very long chain fatty acids (VLCFA) and ABCG5/8 which transports cholesterol, suggesting a potential target for treating dyslipidaemia. The proposed project will investigate the role of ABC transporters in lipid metabolism, using cell models of metabolic tissues (pancreatic beta-cells, muscle cells and hepatocytes), and possibly blood samples from patients with obesity and/or diabetes or cardiovascular disease. The project will elucidate the relative importance of ABC transporters in how these lipids circulate and are metabolised and whether they mediate any of the noxious cellular effects such as lipotoxicity in pancreatic beta-cells and hepatic steatosis.

Neurodegenerative diseases are becoming increasingly prevalent. Advances in modern medicine have led to an increase in life expectancy, which has led to an increase in age-associated disorders, such as dementia. The risk of developing dementia doubles every 5 years after the age of 65 (Corrada et al., 2010, Matthews et al., 2016). Current estimates suggests that AD costs the NHS~£23 billion a year (NHS, 2020). This cost divides into informal care (~42%), social care (~39%) and healthcare (~16%) (Prince, 2014). An improved understanding of the progression and diagnostic features of Alzheimer's disease (AD) will promote earlier diagnosis. There is no cure for AD, with current treatments only acting to limit symptoms and doing little to address the underlying pathology. Current platforms for testing of potential novel therapeutics are outdated and unreliable, resulting in a lack of viable treatments for neurodegenerative diseases such as AD. Animal models and conventional 2D culture platforms fail to recapitulate the complex environment found within the human cortex, an area heavily implicated in the development of age-associated neurodegeneration. Whilst animal models do possess the three-dimensional environment necessary to model neuronal tissue, translation to human physiology is difficult. Conversely in vitro culture systems do possess the necessary humanised components but fail to reproduce the complex 3D morphologies observed in vivo. This project aims to bridge the gap between in vivo and in vitro modelling of the cortex, via creation of a 3D printed tissue engineered construct with physiologically relevant architecture and composition. Utilisation of biomaterials will enable creation of printable hydrogel scaffolds capable of supporting cell culture, while providing mechanical and biochemical cues to cells encapsulated within. A secondary support gel will be utilised to enable printing of low-viscosity bioinks necessary for creation of soft tissues such as the cortex. The ultimate aim of this project is to produce a printed hydrogel construct capable of mimicking the healthy and diseased cortex, while promoting formation of functional neuronal networks in 3D

HYBOCOMIX is focused on a combined theoretical and experimental study of the phase behavior of a blend of an AB diblock copolymer with homopolymer A. where polymer A repeat units can form hydrogen bonds with each other. A completely new self-consistent field theory (SCFT) model will be developed to describe the influence (in such block copolymer systems) of hydrogen bond formation on the block copolymer self-assembly of ordered phases. This model will be exploited to study, both theoretically and experimentally, the phase behavior of an exemplar system; a mixture of polyacrylamide-b-polystyrene (PAM-b-PS) with polyacrylamide (PAM), where polyacrylamide is the hydrogen bonding polymer. The key feature of this interdisciplinary project is in close connection between experiment and theory which will; (i) allow the study of a system that is completely new both from experimental and theoretical points of view and (ii) access model parameters directly from experiment in the framework of a project to provide unequivocal quality for the verification of the new HYBOCOMIX theory. Potential applications of block copolymers with hydrogen bonds are really abundant and include drug delivery applications, self-healing materials, nanolithography and patterning for microelectronics. The success of this project will open the room for future application developments and research of more complex block copolymer systems with hydrogen bonds providing a new widely applicable theoretical method to predict the structure of block copolymers with hydrogen bonds.