How Biomaterials Can Influence Various Cell Types in the Repair and Regeneration of the Heart after Myocardial Infarction

Abstract

The healthy heart comprises many different cell types that work together to preserve optimal function. However, in a diseased heart the function of one or more cell types is compromised which can lead to many adverse events, one of which is myocardial infarction (MI). Immediately after MI, the cardiac environment is characterized by excessive cardiomyocyte death and inflammatory signals leading to the recruitment of macrophages to clear the debris. Proliferating fibroblasts then invade, and a collagenous scar is formed to prevent rupture. Better functional restoration of the heart is not achieved due to the limited regenerative capacity of cardiac tissue. To address this, biomaterial therapy is being investigated as an approach to improve regeneration in the infarcted heart, as they can possess the potential to control cell function in the infarct environment and limit the adverse compensatory changes that occur post-MI. Over the past decade, there has been considerable research into the development of biomaterials for cardiac regeneration post-MI; and various effects have been observed on different cell types depending on the biomaterial that is applied. Biomaterial treatment has been shown to enhance survival, improve function, promote proliferation, and guide the mobilization and recruitment of different cells in the post-MI heart. This review will provide a summary on the biomaterials developed to enhance cardiac regeneration and remodeling post-MI with a focus on how they control macrophages, cardiomyocytes, fibroblasts, and endothelial cells. A better understanding of how a biomaterial interacts with the different cell types in the heart may lead to the development of a more optimized biomaterial therapy for cardiac regeneration.

Keywords: biomaterials; cardiac regeneration; cardiomyocytes; cell response; endothelial cells; fibroblasts; macrophages; myocardial infarction.

Figure 1

Evolution of the infarcted myocardium. MI results in the activation of a multiphase healing process, involving three overlapping phases: the inflammatory, proliferation, and maturation phases. This repair process prevents ventricular rupture, but it is insufficient to protect the myocardium from massive tissue loss and adverse remodeling.

Figure 2

Timing considerations for the application of biomaterial therapies. This schematic summarizes the timeline of post-MI processes and identifies some associated potential cellular targets for biomaterial therapy.

Figure 3

Tissue sections of mouse MI hearts injected with PBS (left) or type 1 collagen biomaterial (right). Note the dilation and thinning of the collagen scar (blue tissue) in the PBS-treated heart, compared to the preservation of wall thickness and viable muscle (red) in the collagen biomaterial-treated heart.