Material-Based Engineering Strategies for Cardiac Regeneration

Abstract

Cardiac tissue is composed of muscle and non-muscle cells, surrounded by extracellular matrix (ECM) and spatially organized into a complex three-dimensional (3D) architecture to allow for coordinated contraction and electrical pulse propagation. Despite emerging evidence for cardiomyocyte turnover in mammalian hearts, the regenerative capacity of human cardiac tissue is insufficient to recover from damage, e.g. resulting from myocardial infarction (MI). Instead, the heart 'repairs' lost or injured tissue by ongoing synthesis and remodeling of scar tissue. Conventional therapies and timely (stem) cell delivery to the injured tissue markedly improve short-term function and remodeling, but do not attenuate later stage adverse remodeling, leading to functional deterioration and eventually failure of the heart. Material-based therapies have been successfully used to mechanically support and constrain the post-MI failing heart, preventing it from further remodeling and dilation. When designed to deliver the right microenvironment for endogenous or exogenous cells, as well as the mechanical and topological cues to guide neo-tissue formation, material-based therapies may even reverse remodeling and boost cardiac regeneration. This paper reviews the up-to-date status of material-based cardiac regeneration with special emphasis on 1) the use of bare biomaterials to deliver passive constraints that unload the heart, 2) the use of materials and cells to create engineered cardiac constructs for replacement, support, or regeneration of damaged myocardium, and 3) the development of bio-inspired and bioactive materials that aim to enhance the endogenous regenerative capacity of the heart. As the therapies should function in the infarcted heart, the damaged host environment and engineered in vitro test systems that mimic this environment, are reviewed as well.

Contact guidance for cardiac tissue engineering using 3D bioprinted gelatin patterned hydrogel

“…Following myocardial infarction (MI), subsequent cell death and matrix remodeling at the MI foci lead to the degradation of fibrillar collagen network and the accumulation of fibrotic scar tissue. This causes mechanical dysfunction of the ventricular wall that can lead to wall thinning, ventricular dilation and the subsequent sequelae of congestive heart failure and myocardial rupture [1,2].…”

Development of Bioactive Patch for Maintenance of Implanted Cells at the Myocardial Infarcted Site

“…Here, we propose a combination of an elastomeric membrane and a self-assembling peptide combining their intrinsic properties and obtaining a more adaptable patch. Different types of material-based approaches have been developed with the aim to improve cardiac function after myocardial infarction to avoid heart failure [62]. One of these approaches is the use of biomaterials to constrain the post-MI failing heart, preventing it from further remodeling and dilatation [63][64][65][66].…”

Recent advances and trends in the applications of MXene nanomaterials for tissue engineering and regeneration

“…157,158 The presence of cardiac tissue engineering may play a crucial role in replacing and maintaining the function of infarcted myocardial tissue and saving the lives of patients. 159,160 Given that the heart needs electrical synaptic interaction between cells to perform physiological function, the biomedical materials used for cardiac tissue engineering must support bioelectric signal conduction and mediate communication between cardiomyocytes (CMs) to realize the synchronous beating of the heart. 8 As a burgeoning 2D nanomaterial with attractive electrical conductivity, hydrophilicity and biocompatibility, MXene is an ideal candidate for cardiac tissue engineering.…”

“…However, due to the lack of cardiac donors and the complications related to immunosuppressive therapy, scientists and surgeons have been looking for new strategies to treat the damaged heart 157,158 . The presence of cardiac tissue engineering may play a crucial role in replacing and maintaining the function of infarcted myocardial tissue and saving the lives of patients 159,160 …”