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.

An Injectable Oxygen Release System to Augment Cell Survival and Promote Cardiac Repair Following Myocardial Infarction

“…Biomaterial therapy with or without growth factors may aid myocardial repair by providing mechanical support to the heart tissue, and affecting tissue inflammation and angiogenesis 17 – 26 . However, the efficacy remains low due to their inability to provide oxygen to metabolic-demanding cardiac cells at early stage of tissue damage 15 , 16 . To address the critical need of oxygen to protect cardiac cells, direct supply of sufficient oxygen in the infarcted area while not provoking deleterious effects is necessary.…”

Biomaterials Loaded with Growth Factors/Cytokines and Stem Cells for Cardiac Tissue Regeneration

“…The effects of hydrogel administration include direct mechanical strengthening [ 36 ], enhanced angiogenesis and regeneration of myocardial tissue, reduced apoptosis and scar size, and improved cardiac function recovery [ 37 ]. Moreover, multiple studies showed that the use of biomaterials alone favorably affects various cells in the post-MI environment such as macrophages, cardiomyocytes, fibroblasts, and endothelial cells [ 38 ]. Recently, hydrogels made of ECM-based biomaterials have drawn attention because of their ability to mimic native ECM and minimize immunogenicity [ 39 ].…”

“…Downstream signaling proceeds via RAS-mitogen-activated protein kinase RAS-(MAPK) and phosphatidylinositide 3-kinase (PI3K) pathways [ 55 ]. In a separate study, sustained and targeted delivery of neuregulin-1β (NRG), which is a member of epidermal growth factor that regulates cardiomyocyte development and proliferation, by a hydroxyethyl methacrylate hyaluronic acid (HEMA-HA) hydrogel, demonstrated a cardioprotective effect and significantly improved ventricular function and structure [ 38 ]. The cardioprotective effect was assessed by the amount of caspase-3 in murine hearts post-MI, which was significantly reduced in the NRG-hydrogel group in comparison to the control groups treated with phosphate-buffered saline, NRG, or hydrogel alone.…”

Current Trends in Biomaterial Utilization for Cardiopulmonary System Regeneration

“…MI involves the pathogenesis of anaerobic respiration, the accumulation of reactive oxygen species, and the death of cardiomyocytes (CM), thus affecting the normal physiological process of the heart [ 5 ]. Post myocardial infarction, the CM extracellular matrix (ECM) undergoes inflammatory, proliferation, and maturation stages of tissue remodeling to support other healthy CM [ 6 , 7 ]. However, the scar tissue or collagen formed by the remodeling of the ECM at the maturation stage does not participate in the concomitant beating of the heart due to loss of organized architecture [ 8 ], which eventually leads to cardiomegaly and, ultimately, heart failure [ 6 ].…”

“…Post myocardial infarction, the CM extracellular matrix (ECM) undergoes inflammatory, proliferation, and maturation stages of tissue remodeling to support other healthy CM [ 6 , 7 ]. However, the scar tissue or collagen formed by the remodeling of the ECM at the maturation stage does not participate in the concomitant beating of the heart due to loss of organized architecture [ 8 ], which eventually leads to cardiomegaly and, ultimately, heart failure [ 6 ]. Present-day remedies like surgical, pharmacological, and endovascular interventions only have soothing purposes and do not address the fundamental flaw, which is the loss of functional CM [ 9 ].…”