Vascular ageing is a key contributor to cardiovascular and cerebrovascular diseases, which collectively account for over 20 million deaths globally each year. As we age, our blood vessels progressively stiffen, losing elasticity and the ability to properly regulate blood flow. This mechanical deterioration alters the behavior of vascular cells and sets the stage for conditions such as hypertension, stroke, and heart failure. Despite its impact, there are currently no effective therapies that directly target the underlying mechanisms of arterial stiffening, due in part to the lack of models that accurately mimic human vascular ageing.
This project aims to bridge that gap by developing a fully bioengineered, human-relevant organ-on-a-chip model of vascular ageing. Our model replicates key microstructural and biomechanical changes seen in ageing vessels, including extracellular matrix (ECM) remodelling, decreased compliance, and altered hemodynamics. Using ECM derived from human cardiac tissue — chemically modified to reflect age-specific properties such as glycation, calcification, and stiffening — we are able to fine-tune the vessel wall’s characteristics in a highly controlled manner. The model also simulates arterial geometry by increasing the medial layer (containing vascular smooth muscle cells, VSMCs) and narrowing the lumen diameter, mirroring the pathological changes observed in aged arteries.
Our platform integrates advanced 3D printing and soft lithography to create customisable vascular chips in under three hours. It supports high-throughput experimentation, enabling up to 24 parallel assays with consistent mechanical properties — ideal for mechanistic studies and drug screening. A unique feature of this system is the incorporation of miniaturised sensors to monitor pressure and mechanical loading in real time, offering dynamic insight into how vascular cells respond to changes in their physical environment.
The model’s co-culture capabilities allow us to investigate how endothelial cells (VECs), VSMCs, immune cells, and ageing ECM interact under flow, stretch, and pressure. By adjusting variables such as ECM stiffness, lipid deposition, and donor age/sex, the platform can be tailored to study patient-specific responses and the role of sex differences in vascular ageing.
Through this physiologically relevant model, we aim to:
- Uncover how mechanical cues and ageing-related ECM changes influence endothelial and immune cell function.
- Identify key mechanotransduction pathways driving inflammation, fibrosis, and vascular dysfunction.
- Establish a screening platform for anti-stiffening therapies and personalised intervention strategies.
This work addresses a critical need for next-generation in vitro tools that move beyond traditional 2D culture or animal models. By mimicking the complexity of human vascular ageing, our platform opens new avenues for research in mechanobiology, vascular disease, and precision therapeutics.
Media
COSMOS: How organ-on-a-chip technology is revolutionising the way we study cardiovascular disease
Key publications
- Endothelial response to the combined biomechanics of vessel stiffness and shear stress is regulated via Piezo1
ACS Applied Materials & Interfaces 2023 Vol 15/Issue 51 - Bioengineered vascular model of foam cell formation
ACS Biomaterials Science & Engineering 2023 Vol 9/Issue 12 - Studying the synergistic effect of substrate stiffness and cyclic stretch level on endothelial cells using an elastomeric cell culture chamber
ACS Applied Materials & Interfaces 2023 Vol 15/Issue 4 - Cyclic stretch enhances neutrophil extracellular trap formation
BMC Biology 2024 Volume 22, article number 209 - Studying the response of aortic endothelial cells under pulsatile flow using a compact microfluidic system
Analytical Chemistry 2019 Vol 91/Issue 18