Funded Project Summary

Award amount: £79,890 Principal Investigator: Dr. Deepak Kalaskar
Institution: Division of Surgery and Interventional Sciences, University College London
Project title: 3D Vascular Model as A Platform to Investigate Vascular Diseases

Project Summary: Cardiovascular diseases are the leading cause of death in industrial nations (Circulation 2017, 135, e146). Our ability to improve existing treatments by identifying new therapeutic targets relies upon understanding the disease pathogenesis, and the underlying biochemical and cellular pathological mechanisms, which remain unknown. Hence developing human relevant in vitro 3D models of vessels which recapitulate the true nature of physiological vascular structures, both anatomically and functionally, is the way forward to solve this clinical problem.

Current studies rely upon 2D cellular models which are too simplistic to capture the complexity and heterogeneity of vascular structures. Preclinical animal models have provided useful insights into cardiovascular disease pathogenesis, but genetic variations with humans have questioned the reliability of the outcomes. To circumvent these issues, we propose to develop 3D in vitro vascular structures using human cells that capture the complex 3D cellular niche, along with biological, mechanical, and chemical cues of the ECM matrix to mimic the native vessels.

This will be achieved using a cross-disciplinary team of leading biomedical scientists, engineers and clinicians working towards designing biological, self-standing, 3D vascular structures that will lay the foundation for studying pathophysiological pathways of several cardiovascular diseases in future- aneurysm, atherosclerosis, calcification and thrombosis. By using 3D bioprinting technology, we aim to achieve spatially controlled hierarchical distributions of multiple cell types to mimic the natural tissue structure of blood vessels. Using novel biomaterials (peptide-based self-assembled bioinks and synthetic hydrogels), we will produce reproducible matrices with optimal microenvironment to support cells to develop into mature vessels. A major part of the study will focus on cell-cell and cell-matrix responses within the construct and how they align, interact and self-organise in response to the environmental stimuli (e.g. Dynamic perfusion using bioreactor) and bioink cues to develop a functional vascular model.