Vascular remodelling is a complex process that involves changes on a biochemical, genetic and structural level. Biological and physiological studies have struggled with deconstructing the complex mechanisms necessary for the tissue to undergo this complex transformation. Pathological remodelling especially after vascular interventions gives rise to a range of complications significantly effecting patients' health and quality of life.

This necessitates the development of an ex-vivo model that can faithfully replicate the vascular environment to facilitate a comprehensive understanding of vascular interventions and their respective mechanistic pathways. This thesis introduces an innovative model that utilises porcine carotid arteries in conjunction with a bespoke 3D-printed flow chamber.

This written work underscores the significant need for an adaptable and user-friendly perfusion system. Current models in use are costly, restrictive, and lack standardisation, thus presenting a considerable barrier to effective and collaborative research. The cornerstone of this project is the development of the EasyFlow system, a flexible, 3D-printed solution engineered to promote transferability and collaboration in the field. Utilising MultiJet Fusion additive manufacturing allowed for rapid prototyping and the manufacturing of complex structures otherwise unattainable with traditional manufacturing techniques.

Subsequent sections thoroughly explore the EasyFlow system's adaptability through a rigorous developmental and testing process. We have identified culture and perfusion conditions suitable for arterial tissue culture, and histological analyses of arteries after a seven days perfusion incubation showed satisfactory cell coverage and viability. Haematoxylin and Eosin highlighted the the maintenance of vascular structure and good tissue fitness even after seven day. Moreover, a coherent endothelial layer identified by CD31 indicated an intact endothelial lining of the lumen, crucial for vascular health and representative ex-vivo models.

EasyFlow inserts' versatility is highlighted by demonstrating its practical applications. Its ability to convert any 50 mL centrifuge tube into a bioreactor showcases its potential to provide an accessible and user-friendly solution for vascular research. By inducing vascular injury using balloon angioplasty, we could also recapitulate early hallmarks of vascular pathogenesis, observing cell activation and tissue remodelling in our perfusion system. We could also observe significant differences in dose-response to endothelial-independent vasodilator indicating the effects of injury on the tissue.

Utilising advanced computational techniques a new and improved analysis pipeline has been created to aid the analyses of large datasets. The generation of standardised and opensource analysis methods facilitated the integration of new tools with collaborators contributing to research across cardiovascular sciences.

The project also acknowledges the challenges encountered during the course of development, primarily finding appropriate manufacturing techniques and materials for a high-pressure system capable of withstanding extended hemodynamic conditions. The solutions derived in response to these obstacles offer critical insights for future developments within the field.

The thesis concludes with a comprehensive review of the findings and exploring potential future research directions. The introduction of the open-source EasyFlow system represents a significant step in overcoming current limitations within vascular research. Its modifiable, cost-effective, and practical design intends to foster a higher degree of collaboration and reproducibility across the research landscape.

In essence, this thesis details the developmental journey and validation of the novel EasyFlow perfusion system, a significant advancement for vascular research. The open-source nature of EasyFlow, coupled with its remarkable versatility, underlines the importance and potential of collaborative, standardised, open-source research tools in accelerating scientific discovery. This platform sets the stage for future investigations into the long-term effects of injury or treatments on tissue, enabling a deeper understanding of vascular pathologies and potential therapeutic strategies.