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Biomimetic Approaches in the Development of Optimised 3D Culture Environments for Drug Discovery in Cardiac Disease
1School of Engineering, University of Leicester, Leicester LE1 7RH, UK.
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.
Insights
Cardiovascular drug discovery faces challenges due to slow progress and high costs. Advanced 3D cell culture models offer more physiologically relevant preclinical screening, improving efficiency and aligning with ethical regulations.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Cardiovascular Research
Background:
- Cardiovascular diseases are a leading global cause of mortality.
- Traditional drug discovery pathways are lengthy, expensive, and prone to high failure rates.
- Increasing regulatory emphasis on the 3Rs (Replacement, Reduction, Refinement) drives innovation in preclinical models.
Purpose of the Study:
- To review challenges in cardiovascular drug discovery.
- To evaluate limitations of conventional preclinical models.
- To highlight successes and potential of advanced in vitro models, particularly 3D cultures and biomimicry.
Main Methods:
- Literature review of cardiovascular drug discovery processes.
- Analysis of in vitro cell culture methodologies (2D vs. 3D).
- Examination of microfluidic and biomimetic approaches for preclinical screening.
Main Results:
- 3D cell cultures demonstrate more physiologically relevant myocyte behavior than 2D cultures.
- 3D models, including microfluidic systems, show promise for enhanced preclinical cardiovascular drug screening.
- Biomimicry offers potential for more accurate disease modeling but faces implementation hurdles.
Conclusions:
- Optimizing in vitro methodologies, especially 3D cultures, is crucial for efficient cardiovascular drug discovery.
- Advanced preclinical models can improve the success rate and reduce costs in drug development.
- Integrating biomimetic principles into commercial drug discovery requires further development and validation.
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