Cardiac Tissue Repair Research Articles

Hydrogels for the Treatment of Myocardial Infarction: Design and Therapeutic Strategies.

Cardiovascular diseases (CVDs) have become the leading global burden of diseases in recent years and are the primary cause of human mortality and loss of healthy life expectancy. Myocardial infarction (MI) is the top cause of CVDs-related deaths, and its incidence is increasing worldwide every year. Recently, hydrogels have garnered great interest from researchers as a promising therapeutic option for cardiac tissue repair after MI. This is due to their excellent properties, including biocompatibility, mechanical properties, injectable properties, anti-inflammatory properties, antioxidant properties, angiogenic properties, and conductive properties. This review discusses the advantages of hydrogels as a novel treatment for cardiac tissue repair after MI. The design strategies of various hydrogels in MI treatment are then summarized, and the latest research progress in the field is classified. Finally, the future perspectives of this booming field are also discussed at the end of this review.

The Long and Winding Road to Cardiac Regeneration

Cardiac regeneration is a critical endeavor in the treatment of heart diseases, aimed at repairing and enhancing the structure and function of damaged myocardium. This review offers a comprehensive overview of current advancements and strategies in cardiac regeneration, with a specific focus on regenerative medicine and tissue engineering-based approaches. Stem cell-based therapies, which involve the utilization of adult stem cells and pluripotent stem cells hold immense potential for replenishing lost cardiomyocytes and facilitating cardiac tissue repair and regeneration. Tissue engineering also plays a prominent role employing synthetic or natural biomaterials, engineering cardiac patches and grafts with suitable properties, and fabricating upscale bioreactors to create functional constructs for cardiac recovery. These constructs can be transplanted into the heart to provide mechanical support and facilitate tissue healing. Additionally, the production of organoids and chips that accurately replicate the structure and function of the whole organ is an area of extensive research. Despite significant progress, several challenges persist in the field of cardiac regeneration. These include enhancing cell survival and engraftment, achieving proper vascularization, and ensuring the long-term functionality of engineered constructs. Overcoming these obstacles and offering effective therapies to restore cardiac function could improve the quality of life for individuals with heart diseases.

Regulatory effect of anisotropic structure on cardiomyocyte maturation

Cardiovascular disease (CVD) is the leading cause of death worldwide. Due to the limited regenerative capacity of the adult heart, treatments based on human pluripotent stem cells (hPSCs) have become the focus of a great deal of research. Human pluripotent stem cell–derived cardiomyocytes (hPSC-CMs) can provide an ideal cell source for CVD model construction, cardiac tissue repair, and drug cardiotoxicology research. However, the immaturity of hPSC-CMs seriously restricts its clinical application. The maturation of cardiomyocytes depends on the orderly arrangement of myofilaments and the increase of the expression of connexin, so the geometric regulation of bioengineering substrate is one of the keys to the maturation of engineered myocardial tissue. This review focuses on the key indicators of anisotropic structures provided by biomaterials to improve the maturation characteristics of cardiomyocytes, so as to promote the maturation of cardiomyocytes, and looks forward to the development direction in this field.

Three-Dimensionally Printed Hydrogel Cardiac Patch for Infarct Regeneration Based on Natural Polysaccharides

Myocardial infarction is one of the more common cardiovascular diseases, and remains the leading cause of death, globally. Hydrogels (namely, those using natural polymers) provide a reliable tool for regenerative medicine and have become a promising option for cardiac tissue regeneration due to their hydrophilic character and their structural similarity to the extracellular matrix. Herein, a functional ink based on the natural polysaccharides Gellan gum and Konjac glucomannan has, for the first time, been applied in the production of a 3D printed hydrogel with therapeutic potential, with the goal of being locally implanted in the infarcted area of the heart. Overall, results revealed the excellent printability of the bioink for the development of a stable, porous, biocompatible, and bioactive 3D hydrogel, combining the specific advantages of Gellan gum and Konjac glucomannan with proper mechanical properties, which supports the simplification of the implantation process. In addition, the structure have positive effects on endothelial cells’ proliferation and migration that can promote the repair of injured cardiac tissue. The results presented will pave the way for simple, low-cost, and efficient cardiac tissue regeneration using a 3D printed hydrogel cardiac patch with potential for clinical application for myocardial infarction treatment in the near future.

Advances in biomaterial-based cardiac organoids

Cardiovascular disease (CVD) is one of the important causes of death worldwide. The incidence and mortality rates are increasing annually with the intensification of social aging. The efficacy of drug therapy is limited in individuals suffering from severe heart failure due to the inability of myocardial cells to undergo regeneration and the challenging nature of cardiac tissue repair following injury. Consequently, surgical transplantation stands as the most efficient approach for treatment. Nevertheless, the shortage of donors and the considerable number of heart failure patients worldwide, estimated at 26 million, results in an alarming treatment deficit, with only around 5000 heart transplants feasible annually. The existing major alternatives, such as mechanical or xenogeneic hearts, have significant flaws, such as high cost and rejection, and are challenging to implement for large-scale, long-term use. An organoid is a three-dimensional (3D) cell tissue that mimics the characteristics of an organ. The critical application has been rated in annual biotechnology by authoritative journals, such as Science and Cell. Related industries have achieved rapid growth in recent years. Based on this technology, cardiac organoids are expected to pave the way for viable heart repair and treatment and play an essential role in pathological research, drug screening, and other areas. This review centers on the examination of biomaterials employed in cardiac repair, strategies employed for the reconstruction of cardiac structure and function, clinical investigations pertaining to cardiac repair, and the prospective applications of cardiac organoids. From basic research to clinical practice, the current status, latest progress, challenges, and prospects of biomaterial-based cardiac repair are summarized and discussed, providing a reference for future exploration and development of cardiac regeneration strategies.

Plant-Derived Biomaterials and Their Potential in Cardiac Tissue Repair.

Cardiovascular disease remains the leading cause of mortality worldwide. The inability of cardiac tissue to regenerate after an infarction results in scar tissue formation, leading to cardiac dysfunction. Therefore, cardiac repair has always been a popular research topic. Recent advances in tissue engineering and regenerative medicine offer promising solutions combining stem cells and biomaterials to construct tissue substitutes that could have functions similar to healthy cardiac tissue. Among these biomaterials, plant-derived biomaterials show great promise in supporting cell growth due to their inherent biocompatibility, biodegradability, and mechanical stability. More importantly, plant-derived materials have reduced immunogenic properties compared to popular animal-derived materials (e.g., collagen and gelatin). In addition, they also offer improved wettability compared to synthetic materials. To date, limited literature is available to systemically summarize the progression of plant-derived biomaterials in cardiac tissue repair. Herein, this paper highlights the most common plant-derived biomaterials from both land and marine plants. The beneficial properties of these materials for tissue repair are further discussed. More importantly, the applications of plant-derived biomaterials in cardiac tissue engineering, including tissue-engineered scaffolds, bioink in 3D biofabrication, delivery vehicles, and bioactive molecules, are also summarized using the latest preclinical and clinical examples.

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention.

Cardiac fibrosis plays an indispensable role in cardiac tissue homeostasis and repair after myocardial infarction (MI). The cardiac fibroblast-to-myofibroblast differentiation and extracellular matrix collagen deposition are the hallmarks of cardiac fibrosis, which are modulated by multiple signaling pathways and various types of cells in time-dependent manners. Our understanding of the development of cardiac fibrosis after MI has evolved in basic and clinical researches, and the regulation of fibrotic remodeling may facilitate novel diagnostic and therapeutic strategies, and finally improve outcomes. Here, we aim to elaborate pathophysiology, examination and intervention of cardiac fibrosis after MI.

M2 Macrophage-Derived sEV Regulate Pro-Inflammatory CCR2+ Macrophage Subpopulations to Favor Post-AMI Cardiac Repair.

Tissue-resident cardiac macrophage subsets mediate cardiac tissue inflammation and repair after acute myocardial infarction (AMI). CC chemokine receptor 2 (CCR2)-expressing macrophages have phenotypical similarities to M1-polarized macrophages, are pro-inflammatory, and recruit CCR2+ circulating monocytes to infarcted myocardium. Small extracellular vesicles (sEV) from CCR2̶ macrophages, which phenotypically resemble M2-polarized macrophages, promote anti-inflammatory activity and cardiac repair. Here, the authors harvested M2 macrophage-derived sEV (M2EV ) from M2-polarized bone-marrow-derived macrophages for intramyocardial injection and recapitulation of sEV-mediated anti-inflammatory activity in ischemic-reperfusion (I/R) injured hearts. Rats and pigs received sham surgery; I/R without treatment; or I/R with autologous M2EV treatment. M2EV rescued cardiac function and attenuated injury markers, infarct size, and scar size. M2EV inhibited CCR2+ macrophage numbers, reduced monocyte-derived CCR2+ macrophage recruitment to infarct sites, induced M1-to-M2 macrophage switching and promoted neovascularization. Analysis of M2EV microRNA content revealed abundant miR-181b-5p, which regulated macrophage glucose uptake, glycolysis, and mitigated mitochondrial reactive oxygen species generation. Functional blockade of miR-181b-5p is detrimental to beneficial M2EV actions and resulted in failure to inhibit CCR2+ macrophage numbers and infarct size. Taken together, this investigation showed that M2EV rescued myocardial function, improved myocardial repair, and regulated CCR2+ macrophages via miR-181b-5p-dependent mechanisms, indicating an option for cell-free therapy for AMI.

Whole-Heart Tissue Engineering and Cardiac Patches: Challenges and Promises.

Despite all the advances in preventing, diagnosing, and treating cardiovascular disorders, they still account for a significant part of mortality and morbidity worldwide. The advent of tissue engineering and regenerative medicine has provided novel therapeutic approaches for the treatment of various diseases. Tissue engineering relies on three pillars: scaffolds, stem cells, and growth factors. Gene and cell therapy methods have been introduced as primary approaches to cardiac tissue engineering. Although the application of gene and cell therapy has resulted in improved regeneration of damaged cardiac tissue, further studies are needed to resolve their limitations, enhance their effectiveness, and translate them into the clinical setting. Scaffolds from synthetic, natural, or decellularized sources have provided desirable characteristics for the repair of cardiac tissue. Decellularized scaffolds are widely studied in heart regeneration, either as cell-free constructs or cell-seeded platforms. The application of human- or animal-derived decellularized heart patches has promoted the regeneration of heart tissue through in vivo and in vitro studies. Due to the complexity of cardiac tissue engineering, there is still a long way to go before cardiac patches or decellularized whole-heart scaffolds can be routinely used in clinical practice. This paper aims to review the decellularized whole-heart scaffolds and cardiac patches utilized in the regeneration of damaged cardiac tissue. Moreover, various decellularization methods related to these scaffolds will be discussed.

Fibrin-Enriched Cardiac Extracellular Matrix Hydrogel Promotes In Vitro Angiogenesis.

Angiogenesis is essential for cardiac repair after myocardial infarction. Promoting angiogenesis has been demonstrated as an effective approach for myocardial infarction treatment. Several different strategies for inducing myocardial angiogenesis have been explored, including exogenous delivery of angiogenic genes, proteins, microRNAs, cells, and extracellular vesicles. Various types of injectable hydrogels have been investigated for cardiac tissue repair. One of the most promising injectable hydrogels in cardiac regeneration is a cardiac extracellular matrix hydrogel that is derived from decellularized porcine myocardium. It can be delivered minimally invasively via transendocardial delivery. The safety and efficacy of cardiac extracellular matrix hydrogels have been shown in small and large animal myocardial infarction models as well as clinical trials. The main mechanisms underlying the therapeutic benefits of cardiac extracellular matrix hydrogels have been elucidated and involved in the modulation of the immune response, downregulation of pathways related to heart failure progression and fibrosis, upregulation of genes important for cardiac muscle contraction, and enhancing cardiomyocyte differentiation and maturation from stem cells. However, no potent capillary network formation induced by cardiac extracellular matrix hydrogels has been reported. In this study, we tested the feasibility of incorporating a fibrin matrix into cardiac extracellular matrix hydrogels to improve the angiogenic properties of the hydrogel. Our in vitro results demonstrate that fibrin-enriched cardiac extracellular matrix hydrogels can induce robust endothelial cell tube formation from human umbilical vein endothelial cells and promote the sprouting of human mesenchymal stem cell spheroids. The obtained information from this study is very critical toward the future in vivo evaluation of fibrin-enriched cardiac extracellular matrix hydrogels in promoting myocardial angiogenesis.

Nanomaterial-Based Electrically Conductive Hydrogels for Cardiac Tissue Repair.

Cardiovascular disease is one of major causes of deaths, and its incidence has gradually increased worldwide. For cardiovascular diseases, several therapeutic approaches, such as drugs, cell-based therapy, and heart transplantation, are currently employed; however, their therapeutic efficacy and/or practical availability are still limited. Recently, biomaterial-based tissue engineering approaches have been recognized as promising for regenerating cardiac function in patients with cardiovascular diseases, including myocardial infarction (MI). In particular, materials mimicking the characteristics of native cardiac tissues can potentially prevent pathological progression and promote cardiac repair of the heart tissues post-MI. The mechanical (softness) and electrical (conductivity) properties of biomaterials as non-biochemical cues can improve the cardiac functions of infarcted hearts by mitigating myocardial cell death and subsequent fibrosis, which often leads to cardiac tissue stiffening and high electrical resistance. Consequently, electrically conductive hydrogels that can provide mechanical strength and augment the electrical activity of the infarcted heart tissue are considered new functional materials capable of mitigating the pathological progression to heart failure and stimulating cardiac regeneration. In this review, we highlight nanomaterial-incorporated hydrogels that can induce cardiac repair after MI. Nanomaterials, including carbon-based nanomaterials and recently discovered two-dimensional nanomaterials, offer great opportunities for developing functional conductive hydrogels owing to their excellent electrical conductivity, large surface area, and ease of modification. We describe recent results using nanomaterial-incorporated conductive hydrogels as cardiac patches and injectable hydrogels for cardiac repair. While further evaluations are required to confirm the therapeutic efficacy and toxicity of these materials, they could potentially be used for the regeneration of other electrically active tissues, such as nerves and muscles.

The Innate Immune System in Cardiovascular Diseases and Its Role in Doxorubicin-Induced Cardiotoxicity

Innate immune cells are the early responders to infection and tissue damage. They play a critical role in the initiation and resolution of inflammation in response to insult as well as tissue repair. Following ischemic or non-ischemic cardiac injury, a strong inflammatory response plays a critical role in the removal of cell debris and tissue remodeling. However, persistent inflammation could be detrimental to the heart. Studies suggest that cardiac inflammation and tissue repair needs to be tightly regulated such that the timely resolution of the inflammation may prevent adverse cardiac damage. This involves the recognition of damage; activation and release of soluble mediators such as cytokines, chemokines, and proteases; and immune cells such as monocytes, macrophages, and neutrophils. This is important in the context of doxorubicin-induced cardiotoxicity as well. Doxorubicin (Dox) is an effective chemotherapy against multiple cancers but at the cost of cardiotoxicity. The innate immune system has emerged as a contributor to exacerbate the disease. In this review, we discuss the current understanding of the role of innate immunity in the pathogenesis of cardiovascular disease and dox-induced cardiotoxicity and provide potential therapeutic targets to alleviate the damage.

Defective efferocytosis of vascular cells in heart disease.

The efficient phagocytic clearance of dying cells and apoptotic cells is one of the processes that is essential for the maintenance of physiologic tissue function and homeostasis, which is termed “efferocytosis.” Under normal conditions, “find me” and “eat me” signals are released by apoptotic cells to stimulate the engulfment and efferocytosis of apoptotic cells. In contrast, abnormal efferocytosis is related to chronic and non-resolving inflammatory diseases such as atherosclerosis. In the initial steps of atherosclerotic lesion development, monocyte-derived macrophages display efficient efferocytosis that restricts plaque progression; however, this capacity is reduced in more advanced lesions. Macrophage reprogramming as a result of the accumulation of apoptotic cells and augmented inflammation accounts for this diminishment of efferocytosis. Furthermore, defective efferocytosis plays an important role in necrotic core formation, which triggers plaque rupture and acute thrombotic cardiovascular events. Recent publications have focused on the essential role of macrophage efferocytosis in cardiac pathophysiology and have pointed toward new therapeutic strategies to modulate macrophage efferocytosis for cardiac tissue repair. In this review, we discuss the molecular and cellular mechanisms that regulate efferocytosis in vascular cells, including macrophages and other phagocytic cells and detail how efferocytosis-related molecules contribute to the maintenance of vascular hemostasis and how defective efferocytosis leads to the formation and progression of atherosclerotic plaques.

Polyelectrolyte Hydrogels for Tissue Engineering and Regenerative Medicine.

Polyelectrolyte hydrogels are emerging materials for tissue engineering and regenerative medicine applications due to their tunable biochemical properties, electrical conductivity, biocompatibility and similar network structure to the extracellular matrix in mammalian bodies. In this review, representative polyelectrolyte hydrogels carrying anionic, cationic, ampholytic, zwitterionic and ionic liquid moieties are systemically cataloged to express their chemical structures and preparation strategies. Recent advance of polyelectrolyte hydrogels in tissue engineering and regenerative medicine for drug delivery, skin healing, bone regeneration, cardiac tissue repair and anti-biofouling coating are also highlighted. Eventually, the outlook and challenges of polyelectrolyte hydrogels and their biomedical material applications are also discussed to offer future directions.

Intracellular Toxic Advanced Glycation End-Products May Induce Cell Death and Suppress Cardiac Fibroblasts.

Cardiovascular disease (CVD) is a lifestyle-related disease (LSRD) induced by the dysfunction and cell death of cardiomyocytes. Cardiac fibroblasts are activated and differentiate in response to specific signals, such as transforming growth factor-β released from injured cardiomyocytes, and are crucial for the protection of cardiomyocytes, cardiac tissue repair, and remodeling. In contrast, cardiac fibroblasts have been shown to induce injury or death of cardiomyocytes and are implicated in the pathogenesis of diseases such as cardiac hypertrophy. We designated glyceraldehyde-derived advanced glycation end-products (AGEs) as toxic AGEs (TAGE) due to their cytotoxicity and association with LSRD. Intracellular TAGE in cardiomyocytes decreased their beating rate and induced cell death in the absence of myocardial ischemia. The TAGE levels in blood were elevated in patients with CVD and were associated with myocardial ischemia along with increased risk of atherosclerosis in vascular endothelial cells in vitro. The relationships between the dysfunction or cell death of cardiac fibroblasts and intracellular and extracellular TAGE, which are secreted from certain organs, remain unclear. We examined the cytotoxicity of intracellular TAGE by a slot blot analysis, and TAGE-modified bovine serum albumin (TAGE-BSA), a model of extracellular TAGE, in normal human cardiac fibroblasts (HCF). Intracellular TAGE induced cell death in normal HCF, whereas TAGE-BSA did not, even at aberrantly high non-physiological levels. Therefore, only intracellular TAGE induced cell death in HCF under physiological conditions, possibly inhibiting the role of HCF.

Micropatterned conductive elastomer patch based on poly (glycerol sebacate)-graphene for cardiac tissue repair

Preparing a micropatterned elastomer film with characteristics that can simulate the mechanical properties, anisotropy, and electroactivity of natural myocardial tissues is crucial in cardiac tissue engineering after myocardial infarction (MI). Therefore, in this study, we developed several elastomeric films with a surface micropattern based on poly (glycerol sebacate) (PGS) and graphene (Gr). These films have sufficient mechanical strength (0.6 ± 0.1–3.2 ± 0.08 MPa) to withstand heartbeats, and the micropatterned structure also satisfies the natural myocardium anisotropy in the transverse and vertical. Moreover, Gr makes these films conductive (up to 5.80 × 10−7 S m−1), which is necessary for the conduction of electrical signals between cardiomyocytes and the cardiac tissue. Furthermore, they have good cytocompatibility and can promote cell proliferation in H9c2 rat cardiomyocyte cell lines. In vivo test results indicate that these films have good biocompatibility. Notably, a film with 1 wt% Gr content (PGS–Gr1) significantly affects the recovery of myocardial function in rats after MI. This film effectively decreased the infarct size and degree of myocardial fibrosis and reduced collagen deposition. Echocardiographic evaluation showed that after treatment with this film, the left ventricular internal dimension (LVID) in systole and LVID in diastole of rats exhibited a significant downward trend, whereas the fractional shortening and ejection fraction were significantly increased compared with the control group. These data indicate that this electroactive micropatterned anisotropic elastomer film can be applied in cardiac tissue engineering.

Inflammation and resolution signaling in cardiac repair and heart failure.

SummaryUnresolved inflammation is a key mediator of advanced heart failure. Especially, damage, pathogen, and lifestyle-associated molecular patterns are the major factors in initiating baseline inflammatory diseases, particularly in cardiac pathology. After a significant cardiac injury like a heart attack, splenic and circulating leukocytes begin a highly optimized sequence of immune cell recruitment (neutrophils and monocytes) to coordinate effective tissue repair. An injured cardiac tissue repair and homeostasis are dependent on clearance of cellular debris where the recruited leukocytes transition from a pro-inflammatory to a reparative program through resolution process. After a cardiac injury, macrophages play a decisive role in cardiac repair through the biosynthesis of endogenous lipid mediators that ensure a timely tissue repair while avoiding chronic inflammation and impaired cardiac repair. However, dysregulation of resolution of inflammation processes due to cardiometabolic defects (obesity, hypertension, and diabetes), aging, or co-medication(s) lead to impaired cardiac repair. Hence, the presented review demonstrates the fundamental role of leukocytes, in particular macrophages orchestrate the inflammation and resolution biology, focusing on the biosynthesis of specialized lipid mediators in cardiac repair and heart failure. This work was supported by research funds from National Institutes of Health (AT006704, HL132989, and HL144788) to G.V.H. The authors acknowledges the use of Servier Medical Art image bank and Biorender that is used to create schematic Figures 1–3.

A novel renal perivascular mesenchymal cell subset gives rise to fibroblasts distinct from classic myofibroblasts

Perivascular mesenchymal cells (PMCs), which include pericytes, give rise to myofibroblasts that contribute to chronic kidney disease progression. Several PMC markers have been identified; however, PMC heterogeneity and functions are not fully understood. Here, we describe a novel subset of renal PMCs that express Meflin, a glycosylphosphatidylinositol-anchored protein that was recently identified as a marker of fibroblasts essential for cardiac tissue repair. Tracing the lineage of Meflin+ PMCs, which are found in perivascular and periglomerular areas and exhibit renin-producing potential, showed that they detach from the vasculature and proliferate under disease conditions. Although the contribution of Meflin+ PMCs to conventional α-SMA+ myofibroblasts is low, they give rise to fibroblasts with heterogeneous α-SMA expression patterns. Genetic ablation of Meflin+ PMCs in a renal fibrosis mouse model revealed their essential role in collagen production. Consistent with this, human biopsy samples showed that progressive renal diseases exhibit high Meflin expression. Furthermore, Meflin overexpression in kidney fibroblasts promoted bone morphogenetic protein 7 signals and suppressed myofibroblastic differentiation, implicating the roles of Meflin in suppressing tissue fibrosis. These findings demonstrate that Meflin marks a PMC subset that is functionally distinct from classic pericytes and myofibroblasts, highlighting the importance of elucidating PMC heterogeneity.

A porcine cholecystic extracellular matrix conductive scaffold for cardiac tissue repair.

Cardiac tissue engineering using cells, scaffolds or signaling molecules is a promising approach for replacement or repair of damaged myocardium. This study addressed the contemporary need for a conductive biomimetic nanocomposite scaffold for cardiac tissue engineering by examining the use of a gold nanoparticle-incorporated porcine cholecystic extracellular matrix for the same. The scaffold had an electrical conductivity (0.74±0.03S/m) within the range of native myocardium. It was a suitable substrate for the growth and differentiation of cardiomyoblast (H9c2) as well as rat mesenchymal stem cells to cardiomyocyte-like cells. Moreover, as an epicardial patch, the scaffold promoted neovascularisation and cell proliferation in infarcted myocardium of rats. It was concluded that the gold nanoparticle coated cholecystic extracellular matrix is a prospective biomaterial for cardiac tissue engineering.

2D Materials for Cardiac Tissue Repair and Regeneration.

Cardiovascular diseases (CVDs) have a massive impact on human health. Due to the limited regeneration capacity of adult heart tissue, CVDs are the leading cause of death and disability worldwide. Even though there are surgical and pharmacological treatments for CVDs, regenerative strategies are the most promising approaches and have the potential to benefit millions of people. As in any other tissue engineering approach, the repair and regeneration of damaged cardiac tissues generally involve scaffolds made up of biodegradable and biocompatible materials, cellular components such as stem cells, and growth factors. This review provides an overview of biomaterial-based tissue engineering approaches for CVDs with a specific focus on the potential of 2D materials. It is essential to consider both physicochemical and immunomodulatory properties for evaluating the applicability of 2D materials in cardiac tissue repair and regeneration. As new members of the 2D materials will be explored, they will quickly become part of cardiac tissue engineering technologies.