# Biomimetic Approaches in the Development of Optimised 3D Culture Environments for Drug Discovery in Cardiac Disease

## TL;DR

This paper reviews how 3D culture models, inspired by natural systems, can improve drug discovery for heart disease by offering more realistic preclinical testing environments.

## Contribution

The paper highlights the role of biomimetic 3D models in overcoming limitations of traditional methods in cardiovascular drug discovery.

## Key findings

- 3D culture models show more physiologically relevant myocyte behavior than 2D models.
- Biomimetic approaches can enhance preclinical drug screening for cardiovascular diseases.
- Implementation of 3D models in commercial drug discovery faces significant challenges.

## Abstract

Cardiovascular disease remains the leading cause of death worldwide, yet despite massive investment in drug discovery, the progress of cardiovascular drugs from lab to clinic remains slow. It is a complex, costly pathway from drug discovery to the clinic and failure becomes more expensive as a drug progresses along this pathway. The focus has begun to shift to optimisation of in vitro culture methodologies, not only because these must be undertaken are earlier on in the drug discovery pathway, but also because the principles of the 3Rs have become embedded in national and international legislation and regulation. Numerous studies have shown myocyte cell behaviour to be much more physiologically relevant in 3D culture compared to 2D culture, highlighting the advantages of using 3D-based models, whether microfluidic or otherwise, for preclinical drug screening. This review aims to provide an overview of the challenges in cardiovascular drug discovery, the limitations of traditional routes, and the successes in the field of preclinical models for cardiovascular drug discovery. It focuses on the particular role biomimicry can play, but also the challenges around implementation within commercial drug discovery.