Advancing 3D Engineered In Vitro Models for Heart Failure Research: Key Features and Considerations

Abstract

Heart failure is characterized by intricate myocardial remodeling that impairs the heart's pumping and/or relaxation capacity, ultimately reducing cardiac output. It represents a major public health burden, given its high prevalence and associated morbidity and mortality rates, which continue to challenge healthcare systems worldwide. Despite advancements in medical science, there are no treatments that address the disease at its core. The development of three-dimensional engineered in vitro models that closely mimic the (patho)physiology and drug responses of the myocardium has the potential to revolutionize our insights and uncover new therapeutic avenues. Key aspects of these models include the precise replication of the extracellular matrix structure, cell composition, micro-architecture, mechanical and electrical properties, and relevant physiological and pathological stimuli, such as fluid flow, mechanical load, electrical signal propagation, and biochemical cues. Additionally, to fully capture heart failure and its diversity in vivo, it is crucial to consider factors such as age, gender, interactions with other organ systems and external influences-thereby recapitulating unique patient and disease phenotypes. This review details these model features and their significance in heart failure research, with the aim of enhancing future platforms that will deepen our understanding of the disease and facilitate the development of novel, effective therapies.

Keywords: 3D models; biomimetic scaffolds; cardiac fibrosis; cardiac tissue engineering; cell maturation; extracellular matrix; heart failure; in vitro modeling; myocardial remodeling; translational research.

Figure 1

Comparison of ECM features in healthy and HF engineered heart tissues (EHTs).

Figure 2

Comparison of scaffold properties in cardiac tissue engineering. Decm = decellularized extracellular matrix, PEG = polyethylene glycol, PGLA = poly(lactic-co-glycolic acid), PGA = polyglycolic acid, PLA = polylactic acid, Gel-MA = gelatin methacryloyl. Created in BioRender.