Developing Selective Immunomodulatory Solutions for Cardiovascular Devices

Abstract

Cardiovascular devices such as stents, balloons and artificial heart valves are foundational in the treatment of cardiovascular diseases, yet their long-term performance is limited by local inflammatory responses. Depending on the device and its location within the vasculature, these responses can manifest in distinct forms of maladaptive tissue remodelling including fibrosis, neointimal hyperplasia, and calcification. Contemporary devices mitigate downstream consequences of this response by eluting anti-proliferative or cytotoxic drugs, but they do not address the underlying inflammation nor actively promote healing around the device, resulting in poor durability. Although inflammation has long been considered a central driver of device failure, it has remained a challenging therapeutic target due to off-target risks associated with systemic immunosuppression. This thesis explored strategies to overcome this challenge by combining selective immunomodulation as a new drug strategy with advanced localised delivery platforms to enhance cardiovascular device longevity.