Industry Partner: AstraZeneca

Skin toxicity remains one of the most challenging dose-limiting side effects of oncology drugs, especially targeted therapies. Existing in vitro and animal models lack sufficient predictivity for clinical toxicity, hindering efforts to balance efficacy with safety in drug development. Development of validated human skin-on-chip platforms that mimic key toxicologic responses addresses this gap by providing industry and academia with more predictive tools, supporting safer and more effective anti-cancer drug discovery while minimising reliance on animal models.  The overall aim of this PhD studentship is to develop a next-generation vascularised skin-on-chip platform that accurately replicates essential skin toxicity responses to cancer therapeutics. 

The project will leverage QMUL’s state-of-the-art human skin models, which consist of a 3D printed skin equivalents containing keratinocytes, fibroblasts, endothelial cells, and resident macrophages. Building on this design, the proposed project will optimise the biophysical properties, perfusion and dosing of key drugs, establish robust toxicity readouts, and explore potential mechanisms of action.  In addition, new technological advances will be implemented through the engineering of a dual-chip system that enables simultaneous prediction of drug toxicity in the skin-on-chip device and therapeutic efficacy in cancer models, thereby facilitating direct assessment of the therapeutic index and supporting optimised anti-cancer drug selection. 

In collaboration with AstraZeneca, a major focus of the project will be to validate the skin-on-chip system with clinically relevant oncology agents to demonstrate correlation between in vitro readouts—target engagement, viability, proliferation, cytokine profiles, tissue integrity, immune activation—and clinical skin toxicity risk.

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Targeting inflammatory pathways in asthma utilising an alveolar lung-on-a-chip model 

Industry Partner: Chiesi Farmaceutici

Asthma is a chronic lung condition and currently there are 7.2million people in the UK with the disease. Asthma is an inflammatory disease of the lung which results in airway remodelling, loss of elasticity, airway hyperresponsiveness and mucus hyperplasia. Asthma pathology is driven by a combination of lung stromal cells such as epithelial cells as well as lung resident immune cells such as macrophages, mast cells and T cells.  

Currently scientists study asthma either using mouse models of disease or static air-liquid-interphase culture systems – limitations to both these models mean they do not fully recapitulate human asthmatic lung mechanobiology. Therefore, there is a clear unmet need to develop more physiological lung models which model the human asthmatic lung including, relevant biophysical cues and immune cells. Preliminary data has shown that the EMULATE alveolar chip model recreates the human lung most effectively, with immune cells flowing through the endothelium and stretch caused by breathing recreated.

The overarching aim of this project is to engineer a novel asthma model using the EMULATE alveolar-chip platform.

To achieve this the following experimental aims are proposed:

1. Adapt the EMULATE alveolar-chip to model asthma, utilising asthma patient cell lines and disease mimicking biophysical cues (impaired stretch and fluid flow).

2. Incorporate myeloid cells into the model to make the asthma EMULATE model immune responsive.

3. Investigate the interplay between mechanical cues and immune cells in asthma disease severity/progression.

4. Test anti-inflammatory drugs using the immune responsive asthma EMULATE model to determine if inflammatory pathways are reduced.

Overall, this project will establish a novel asthma lung on a chip model with an immune cell component which can be used to test novel anti-inflammatory therapies. In addition, the studies will provide new insight into the mechanobiology of asthma progression.

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Development of an immune-infiltrated adipose tissue-on-a-chip model for interactions between inflammation and dysfunction 

Supervisors: Dr Claire Villette, Dr Stefaan Verbruggen

Industry Partner: CN-Bio

Industry Partner: Cellink

Organ-chip models offer exciting opportunity to unlock discovery science and pre-clinical testing, by providing more human-relevant models of disease. However, the design of appropriate niche environments within models to maintain physiological or pathological cell phenotype and function is crucial for their success.

Here we focus on the design of appropriate niche environments to capture the tendon-bone junction. The tendon-bone interface is a common site of painful, debilitating injury, where a vicious cycle of inflammation, tissue remodelling and interface stiffening drives further degeneration. We currently have no clear treatments for injury at the tendon-bone interface, but models to unpick and thus modulate the interplay between inflammation and tissue stiffening offer exciting potential for new drug targets.

In this project, we will work with the BIONOVA X 3D bioprinter (supplied by industrial partner CELLINK), to select and optimise printable hydrogels and light patterning approaches, to capture the tendon-bone stiffness gradient, and to integrating growth factor gradients which capture the biological gradient between the tissues. We will drive inflammation within the model, then utilise printing approaches to modulate the tissue stiffness at the junction, and explore how this impacts injury progression, driving mechanistic understanding of disease progression and identifying potential treatment targets for tendon-bone injuries.

CELLINK’s focus is in developing approaches to bioprint within organ-chip platforms. They will provide technical expertise, supervision and a placement focused on optimising the printing approaches, and will also work with us to explore how we translate these to support the development of a range of different models.

Industry Partner: Peptimatrix

The extracellular matrix (ECM) is a three-dimensional (3D), bioactive, instructive network that regulates cell behaviour through biochemical and biophysical cues. The ECM plays a crucial role in musculoskeletal (MSK) tissue development, function and dysfunction and should be considered an essential component in the design of Organ-on-a-Chip (OoC) models

Paradoxically, given the animal replacement potential of OoC, many of the hydrogels that are currently used to mimic the 3D ECM in MSK OoC systems are still animal-derived e.g. Matrigel™ and collagen type 1. This therefore represents a significant, but largely overlooked, source of animal use that necessitates replacement. In addition, animal-derived hydrogels are ill-defined, poorly-customisable, prone to batch-to-batch variability, and demonstrate insufficient mechanical properties. There is an urgent need for new, characterised, customisable and animal-free hydrogels for use in OoC models.

This project seeks to address this requirement using PeptiMatrix™, a fully synthetic and customisable peptide hydrogel platform designed for 3D cell culture. PeptiMatrix™ is available in a range of different stiffnesses, and with a range of functional augmentations. This studentship will evaluate the feasibility of using these formulations in a number of different OoC systems (Emulate, MIMETAS, BiomimX), and to model a number of MSK tissues (synovium, cartilage, bone). The project will assess the ability of these gels to maintain MSK cell viability and phenotype, transmit mechanical strain and ultimately to generate physiologically-relevant, engineered MSK tissues within OoC.

With technical and strategic consultancy provided by the PeptiMatrix™ team, this project could re-define 3D tissue microenvironments within MSK OoC. In addition, the applicability of these new materials and methodologies will not be limited to MSK tissues and has the potential for wide reaching impact across the OoC field.