Abstract
Heart failure (HF) after myocardial infarction (MI) due to blockage of coronary arteries is a major public health issue. MI results in massive loss of cardiac muscle due to ischemia. Unfortunately, the adult mammalian myocardium presents a low regenerative potential, leading to two main responses to injury: fibrotic scar formation and hypertrophic remodeling. To date, complete heart transplantation remains the only clinical option to restore heart function. In the last two decades, tissue engineering has emerged as a promising approach to promote cardiac regeneration. Tissue engineering aims to target processes associated with MI, including cardiomyogenesis, modulation of extracellular matrix (ECM) remodeling, and fibrosis. Tissue engineering dogmas suggest the utilization and combination of two key components: bioactive molecules and biomaterials. This chapter will present current therapeutic applications of biomaterials in cardiac regeneration and the challenges still faced ahead. The following biomaterial-based approaches will be discussed: Nano-carriers for cardiac regeneration-inducing biomolecules; corresponding matrices for their controlled release; injectable hydrogels for cell delivery and cardiac patches. The concept of combining cardiac patches with controlled release matrices will be introduced, presenting a promising strategy to promote endogenous cardiac regeneration.
Highlights
Heart failure (HF) is a leading, growing public health problem, affecting millions of people worldwide (Laflamme and Murry, 2011)
It was Biomaterial Approach for Cardiac Regeneration shown that neonatal mammalian hearts, including mice (Porrello et al, 2011, 2013), rats, and even humans (Haubner et al, 2016), can exhibit the ability to regenerate and functionally recover in several injury models, in a limited time window immediately after birth
Genetic fate mapping in zebrafish and neonatal mice revealed that endogenous heart repair was achieved by the proliferation of pre-existing cardiomyocytes (CMs), not by the mobilization of undifferentiated precursors (Jopling et al, 2010; Kikuchi et al, 2010)
Summary
Heart failure (HF) is a leading, growing public health problem, affecting millions of people worldwide (Laflamme and Murry, 2011). It was demonstrated in an ischemia mice model that the marginally improved heart function after stem cell therapy is mostly attributed to the induction of acute immune response rather than proliferation of transplanted or endogenous CMs. Vagnozzi et al (2019) showed that the functional benefit underlying this strategy is inflammatory-based wound healing and attenuation of fibrosis, suggesting that the moderate improvement in cardiac function observed in the past corresponds better with the paracrine hypothesis.
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