Cardiac Regeneration Research Articles

Injectable Hydrogels in Cardiovascular Tissue Engineering.

Heart problems are quite prevalent worldwide. Cardiomyocytes and stem cells are two examples of the cells and supporting matrix that are used in the integrated process of cardiac tissue regeneration. The objective is to create innovative materials that can effectively replace or repair damaged cardiac muscle. One of the most effective and appealing 3D/4D scaffolds for creating an appropriate milieu for damaged tissue growth and healing is hydrogel. In order to successfully regenerate heart tissue, bioactive and biocompatible hydrogels are required to preserve cells in the infarcted region and to bid support for the restoration of myocardial wall stress, cell survival and function. Heart tissue engineering uses a variety of hydrogels, such as natural or synthetic polymeric hydrogels. This article provides a quick overview of the various hydrogel types employed in cardiac tissue engineering. Their benefits and drawbacks are discussed. Hydrogel-based techniques for heart regeneration are also addressed, along with their clinical application and future in cardiac tissue engineering.

Cellular senescence is required for cardiac regeneration.

Cellular senescence is required for cardiac regeneration.

Some Numerical Results on Chemotactic Phenomena in Stem Cell Therapy for Cardiac Regeneration

Biological models for cardiac regeneration and remodeling, along with the effects of cytokines or chemokines during the therapy with mesenchymal stem cells after a myocardial infarction, are of crucial importance for understanding the complex underlying mechanisms. This paper presents a mathematical model composed of three coupled partial differential equations that describes the dynamics of stem cells, nutrients and chemokines, highlighting the fundamental role of the chemokines during the myocardial tissue regeneration process. The system is solved numerically using mimetic difference operators and the MOLE library for MATLAB. The results show the tissue regeneration process in the necrotic part closest to the cell implantation area.

Cardiac regeneration and stem cell therapy through the view of design-driven clinical applications cardiology-related practice: current knowledge and future prospects

Cardiac regeneration and stem cell therapy through the view of design-driven clinical applications cardiology-related practice: current knowledge and future prospects

Global ischemia induces stemness and dedifferentiation in human adult cardiomyocytes after cardiac arrest

Global ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1α. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.

Injectable biodegradable microcarriers for iPSC expansion and cardiomyocyte differentiation.

Cell therapy is a potential novel treatment for cardiac regeneration and numerous studies have attempted to transplant cells to regenerate the myocardium lost during myocardial infarction. To date, only minimal improvements to cardiac function have been reported. This is likely to be the result of low cell retention and survival following transplantation. This study aimed to improve the delivery and engraftment of viable cells by using an injectable microcarrier that provides an implantable, biodegradable substrate for attachment and growth of cardiomyocytes derived from induced pluripotent stem cells (iPSC). We describe the fabrication and characterisation of Thermally Induced Phase Separation (TIPS) microcarriers and their surface modification to enable iPSC-derived cardiomyocyte attachment in xeno-free conditions is described. The selected formulation resulted in iPSC attachment, expansion, and retention of pluripotent phenotype. Differentiation of iPSC into cardiomyocytes on the microcarriers is investigated in comparison with culture on 2D tissue culture plastic surfaces. Microcarrier culture is shown to support culture of a mature cardiomyocyte phenotype, be compatible with injectable delivery, and reduce anoikis. The findings from this study demonstrate that TIPS microcarriers provide a supporting matrix for culturing iPSC and iPSC-derived cardiomyocytes in vitro and are suitable as an injectable cell-substrate for cardiac regeneration.

Non-human primate studies for cardiomyocyte transplantation-ready for translation?

Non-human primates (NHP) are valuable models for late translational pre-clinical studies, often seen as a last step before clinical application. The unique similarity between NHPs and humans is often the subject of ethical concerns. However, it is precisely this analogy in anatomy, physiology, and the immune system that narrows the translational gap to other animal models in the cardiovascular field. Cell and gene therapy approaches are two dominant strategies investigated in the research field of cardiac regeneration. Focusing on the cell therapy approach, several xeno- and allogeneic cell transplantation studies with a translational motivation have been realized in macaque species. This is based on the pressing need for novel therapeutic options for heart failure patients. Stem cell-based remuscularization of the injured heart can be achieved via direct injection of cardiomyocytes (CMs) or patch application. Both CM delivery approaches are in the late preclinical stage, and the first clinical trials have started. However, are we already ready for the clinical area? The present review concentrates on CM transplantation studies conducted in NHPs, discusses the main sources and discoveries, and provides a perspective about human translation.

MiR-1 as a Key Epigenetic Regulator in Early Differentiation of Cardiac Sinoatrial Region.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation was analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors-of both primitive endocardial tubes-committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant novelty, our results revealed that miR-1 increased Amhc1, Tbx5 and Gata4, while this microRNA diminished Mef2c and Cripto expressions during early differentiation of the cardiac sinoatrial region. Furthermore, we observed in this developmental context that miR-1 upregulated CrabpII and Rarß and downregulated CrabpI, which are three crucial factors in the retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacted with Hdac4 and Calm1/Calmodulin, as well as with Erk2/Mapk1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in the early differentiation of the cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Reversine enhances the conversion of dedifferentiated fat cells into mature cardiomyocytes.

There is an essential need for cardiomyocyte regeneration among patients with heart failure. Transplantation of dedifferentiated fat (DFAT) cells may lead to an improvement of cardiomyocyte regeneration among heart failure patients. We believe that DFAT cells are promising candidate cell sources for cardiac regeneration. However, the pathway underlying how DFAT cells of the adipose lineage differentiate into mature cardiomyocytes isn't fully understood. We conducted an experimental laboratory study on isolated DFAT cells from adipose tissue of healthy adults. Then, we treated cells with different concentrations of reversine (10, 20 and 40 nM), and performed RNA extraction and cDNA synthesis. Next, we used a ceiling culture method based on the buoyancy properties of mature lipid-filled adipocytes. Stemness expression (Octamer-binding transcription factor 4 [Oct4], brachyury, Fetal liver kinase 1 [Flk-1]) was quantified by reverse transcription-quantitative (RT-q)PCR, while cardiomyocyte expression (Transcription factor GATA-4 [GATA4] and cardiac troponin T [cTnT]) was quantified by immunocytochemistry. ANOVA with Tukey's post-hoc found that 10 nM reversine increased greater Flk-1 expression compared to the control group (MD: 5.037 + 0.998; p < 0.001), but there were no significant changes among Oct4 (MD: 0.013 + 1.244; p = 0.99) and brachyury expression (MD: 0.157 + 0.084; p = 0.252). Kruskal-Wallis revealed that the expression of GATA4 (1.65 [0.41-1.98] to 0.015 [0.007-0.034]; p =0.017) reduced significantly from day 7 until day 21 and cTnT (5.07 [6.62-8.91] to 8.22 [6.81-9.40]; p= 0 .001) increased significantly from day 7 until day 21. Reversine could increase the expression of Flk-1, but it was unable to stimulate the expression of Oct4 and brachyury related to cell stemness. An optimal concentration of 10 nM reversine may have the greatest effect on enhancing the differentiation of DFAT cells into mature cardiomyocytes, as indicated by higher cTnT expression between cells.

Importance of Biopolymers in Pharmaceutical and Medical Fields

Biopolymers have gained significant traction in the pharmaceutical and medical fields due to their unique properties and versatile applications. These naturally derived polymers exhibit remarkable characteristics such as biodegradability, biocompatibility, renewability, affordability, and availability. Their role in tissue engineering, wound healing, and biosensor development has been extensively explored. In tissue engineering, biopolymers serve as scaffolds or matrices, supporting cell growth, proliferation, and differentiation for both hard and soft tissue regeneration. Hard tissue scaffolds often incorporate biopolymers like collagen, chitosan, and gelatin, combined with bioactive ceramics like hydroxyapatite, mimicking the natural composition of bone. Soft tissue scaffolds employ biopolymers such as collagen, gelatin, elastin, and alginate, fabricated into hydrogels, fibrous meshes, or porous structures for applications like skin, vascular, cardiac, and nerve tissue regeneration. Biopolymers have demonstrated promising potential in promoting wound healing and tissue repair, creating moist wound dressings, absorbing exudates, and providing a favorable environment for tissue regeneration. Biopolymers like collagen, chitosan, and alginate have been investigated for this purpose. In biosensor development, biopolymers offer biocompatibility and the ability to immobilize biomolecules such as enzymes, antibodies, or nucleic acids, serving as matrices for biological recognition elements while maintaining their activity and stability

Advancements in tissue engineering for cardiovascular health: a biomedical engineering perspective.

Myocardial infarction (MI) stands as a prominent contributor to global cardiovascular disease (CVD) mortality rates. Acute MI (AMI) can result in the loss of a large number of cardiomyocytes (CMs), which the adult heart struggles to replenish due to its limited regenerative capacity. Consequently, this deficit in CMs often precipitates severe complications such as heart failure (HF), with whole heart transplantation remaining the sole definitive treatment option, albeit constrained by inherent limitations. In response to these challenges, the integration of bio-functional materials within cardiac tissue engineering has emerged as a groundbreaking approach with significant potential for cardiac tissue replacement. Bioengineering strategies entail fortifying or substituting biological tissues through the orchestrated interplay of cells, engineering methodologies, and innovative materials. Biomaterial scaffolds, crucial in this paradigm, provide the essential microenvironment conducive to the assembly of functional cardiac tissue by encapsulating contracting cells. Indeed, the field of cardiac tissue engineering has witnessed remarkable strides, largely owing to the application of biomaterial scaffolds. However, inherent complexities persist, necessitating further exploration and innovation. This review delves into the pivotal role of biomaterial scaffolds in cardiac tissue engineering, shedding light on their utilization, challenges encountered, and promising avenues for future advancement. By critically examining the current landscape, we aim to catalyze progress toward more effective solutions for cardiac tissue regeneration and ultimately, improved outcomes for patients grappling with cardiovascular ailments.

Stem cell therapy for cardiac regeneration: key points

Cardiovascular diseases are a leading cause of disability and mortality among the working population, necessitating the development and implementation of new, more effective treatment and rehabilitation methods for such patients, including the use of modern cellular and tissue technologies. In this review, an analysis and summary of research results over the past decades regarding the effectiveness of various types of stem cells in heart pathology were conducted. Priority directions include the search for more accessible and safe sources of stem cells, the development of new effective methods for their cultivation, and the use of scaffolds for transplantation. Given the pathogenetic mechanisms of cardiovascular pathology and myocardial regeneration, particular interest for clinical application is drawn to tissue-specific progenitors from the myocardium for replacing injured cardiomyocytes, endothelial progenitors for correcting accompanying endothelial dysfunction, and multipotent mesenchymal cells of various origins with low immunogenicity that exhibit trophic, anti-inflammatory, immunomodulatory, and anti-apoptotic effects. Questions regarding the optimal method, dose, and frequency of stem cell administration, as well as the standardization of criteria for their quality and effectiveness, remain open. Additionally, the combined use of different types of stem cells may serve as a new priority strategy in assessing the effectiveness and safety of cell therapy, especially considering the paradigm of repeated transplantation. The successful translation of obtained preclinical results into further large, well-planned, placebo-controlled clinical trials will enhance the safety and effectiveness of cell therapy for cardiovascular diseases, which is one of the current challenges of modern regenerative medicine.

Exploring the interactions between cardiomyocytes and endothelial cells to induce cardiac revascularization and regeneration

Abstract Funding Acknowledgements None. Background The adult heart is unable to regenerate after ischemic injury, primarily due to the incapacity of cardiomyocyte (CM) to re-enter in the cell cycle and endothelial cells (EC) to form new vessels. Interestingly, our recent data have unveiled that the decline of CM proliferation after birth is paralleled by a reduction in angiogenic potential. Nevertheless, the precise mechanisms governing angiogenesis inhibition in the adult heart remain elusive. We hypothesize that the terminal differentiation of CMs after birth leads to the paracrine suppression of EC proliferation. Purpose This study aims to identify membrane or secreted factors produced by adult CMs that inhibit EC proliferation and vessel formation in order to create new therapeutic strategies to induce cardiac revascularization and regeneration. Material and Methods To validate our hypothesis, ECs were co-cultured with CMs at distinct differentiation stages. Leveraging existing RNA sequencing datasets, we generated an interactome between ligands produced by CMs and receptors expressed by cardiac ECs. Through gain and loss of function studies, we identified pivotal anti-angiogenic factors and subsequently knocked-out the corresponding genes in Cas9 mice, with the aim of rescue the angiogenic potential of the adult heart. Concurrently, we assessed the ability of miR199a, a pro-proliferative miRNA known for inducing CM de-differentiation, to elicit EC proliferation and angiogenesis when delivered to the adult heart together with VEGF-A, utilizing adeno-associated viral vectors. Results Our findings revealed that adult CMs impaired EC proliferation. Comprehensive analysis identified 20 membrane and secreted factors, establishing 118 ligand-receptor interactions between CMs and ECs. Notably, KCNJ11 and CD74 emerged as key factors, as validated through gain and loss of function experiments. In vivo knockout of these genes in CMs led to significant increase in EC proliferation and the formation of neo-vessels. Furthermore, CM de-differentiation induced by miR199a demonstrated the capacity to promote EC proliferation and neo-vessel formation upon VEGF-A stimulation. Conclusions Collectively, this work demonstrated that fully mature CMs have a role in limiting angiogenic potential of the adult heart, likely explaining the failure of therapeutic angiogenesis approaches attempted so far. Our results suggest that innovative strategies targeting CM-EC cross-talk or inducing partial CM de-differentiation may open new therapeutic avenues in the field of cardiac regeneration.Adult CMs inhibit EC proliferationCMdedifferentiation rescues angiogenesis

Transcriptomic insights into cardiac healing - unveiling promising targets for effective gene therapies in diseased hearts

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation Identifying therapeutical target genes is the first step towards developing new gene therapies to promote cardiac repair after injury. In the last decades, despite the many steps forward, not a single therapy has shown to be effective and suitable for human treatment of the injured heart. Considering that cardiac diseases represent one of the most prevalent causes of morbidity, disability, and mortality in the world, it is, therefore, essential to develop new and improved therapies to induce cardiac regeneration. In this study, we aimed to identify novel therapeutical targets that could be used for future purposes of cardiac gene therapy. Unlike previous studies that investigated fetal hearts that are physiologically and functionally different from mature hearts, we focused on investigating adult human hearts that we collected from human donors with post-mortem time below 5 hours. Samples of left ventricles were molecularly and morphologically characterized for the presence of stress, cardiac damage, and cardiac fibrosis. Results of the molecular analyses were cross-referenced with the donors' medical history to classify each specimen as "control" or "diseased." Next, we performed single nuclei RNA sequencing of samples of the left ventricle from 2 "control" and 3 "diseased" hearts. Due to the adult tissue's complexity and the specimen's high-fiber content, we optimized the nuclei isolation protocol. Eventually, we successfully sequenced an average of 8.000 nuclei per sample with a gene coverage of approximately 800 genes per nucleus, identifying, via unsupervised cluster analysis, 17 different cell populations. In cardiomyocytes, we identified over 500 genes differentially expressed in diseased hearts when compared to healthy controls. Among these genes, we discovered several novel target genes whose expression is increased only in diseased cardiomyocytes. Gene ontology analysis of the known interactors of the newly identified target genes shows enrichment in terms such as sarcomere organization, muscle contraction, mitochondrial energetics, calcium handling, and fatty acid metabolism. Currently, we are investigating the molecular effects of the gain and loss of function of these genes in healthy iPS-derived cardiomyocytes and human-derived myocardial tissue slices to better understand their role in the pathophysiology of the adult human heart. From a therapeutic perspective, our ongoing research holds promises for developing new and improved intervention therapies to promote cardiac regeneration.

Acquired control over proliferation and differentiation of ventricular cardiomyocytes to break down the mechanisms of cardiac repair

Abstract Funding Acknowledgements None. Loss of myocardial tissue remains a leading cause of morbidity and mortality by causing heart rhythm disturbances and heart failure. The (pre-)clinical effects of inducing cardiac regeneration by cardiac cell therapy have been disappointing. In order to find new curative options for these disabling cardiac diseases a shift of focus towards steering the heart to regenerate itself is needed. The aim of this study was to generate a robust ventricular cardiomyocyte model in which proliferation and differentiation could be tightly controlled to investigate cardiac regeneration. To accomplish this we have generated a line of immortalized neonatal rat ventricular cardiomyocytes (nrVMs) through expression of the cell cycle regulators cyclin-dependent kinase 4 and cyclin D1 (CDK4-D1). The CDK4-D1 expressing nrVMs were positive for the proliferation marker Ki67 in contrast to control nrVMs. Cardiomyogenic differentiation could still be induced after multiple passages (&amp;gt; passage 10) as evidenced by immunocytochemistry and optical voltage mapping. These contractile and excitable cells were indeed positive for the cardiac-specific sarcomeric proteins alpha actinin and troponin T in a sarcomeric pattern similar to native nrVMs. Passaging of the control nrVM cultures, however, ultimately led to a senescent cell population lacking sarcomeric markers after passage 3. Electrophysiological analysis of immortalized monolayers, after inducing cardiomyogenic differentiation, showed not only uniform propagation of electrical signal throughout the cultures, but also re-entrant activity although at low frequency. In conclusion, these data show that were able to immortalize ventricular cardiomyocytes by preserving their contractile and excitable phenotype upon significant expansion. Further optimisation of this model will lead to a research model of ventricular cardiomyocytes which will give us the opportunity to unravel the process of cardiomyogenesis and uncover mechanisms which could allow us to enhance the ability of the heart to regenerate itself.

A site-specific phosphorylation in FSTL1 determines its promigratory role in wound healing

Follistatin like-1 (FSTL-1) is a secreted glycoprotein of mesenchymal in origin. In human skin, FSTL1 is upregulated in the epidermal keratinocytes upon acute injury and is required for the migration of keratinocytes. Failure to upregulate FSTL1 leads to the lack of keratinocyte migration and the non-healing nature of diabetic foot ulcer (DFU). FSTL1 undergoes extensive post-translational modification (PTM) at specific residues. Glycosylation at N144, N175 and N180, are the only experimentally demonstrated PTM in FSTL1, wherein, N180 and N144 glycosylations have been found to be critical for its function in cardiac tissue regeneration and pre-adipocyte differentiation, respectively. However, it is not known if PTMs other than glycosylation occurs in FSTL1 and how it impacts its pro-migratory function. Using in-silico analysis of mass spectrometric datasets, we found a novel PTM, namely, Serine 165 (S165) phosphorylation in FSTL1. To address the role of S165 phosphorylation in its pro-migratory function, a phosphorylation defective mutant of FSTL1 (S165A) was constructed by converting serine 165 to alanine and over expressed in 293T cells. S165A mutation did not affect the secretion of FSTL1 in vitro. However, S165A abolished the pro-migratory effect of FSTL1 in cultured keratinocytes likely via its inability to facilitate ERK signaling pathway. Interestingly, bacterially expressed recombinant FSTL1, trans-dominantly inhibited wound closure in keratinocytes highlighting the prime role of FSTL1 phosphorylation for its pro-migratory function. Further, under high glucose conditions, which inhibited scratchwound migration of keratinocytes, we noticed a significant decrease in S165 phosphorylation. Taken together, our results reveal a hitherto unreported role of FSTL1 phosphorylation PTM with profound implications in wound healing.

Stem Cell Angiogenesis in Myocardial Infraction Treatment: Efficacy and Future Directions

Stem Cell Angiogenesis in Myocardial Infraction Treatment: Efficacy and Future Directions

Metabolic Reprogramming: A Byproduct or a Driver of Cardiomyocyte Proliferation?

Defining mechanisms of cardiomyocyte proliferation should guide the understanding of endogenous cardiac regeneration and could lead to novel treatments for diseases such as myocardial infarction. In the neonatal heart, energy metabolic reprogramming (phenotypic alteration of glucose, fatty acid, and amino acid metabolism) parallels cell cycle arrest of cardiomyocytes. The metabolic reprogramming occurring shortly after birth is associated with alterations in blood oxygen levels, metabolic substrate availability, hemodynamic stress, and hormone release. In the adult heart, myocardial infarction causes metabolic reprogramming but these changes cannot stimulate sufficient cardiomyocyte proliferation to replace those lost by the ischemic injury. Some putative pro-proliferative interventions can induce the metabolic reprogramming. Recent data show that altering the metabolic enzymes PKM2 [pyruvate kinase 2], LDHA [lactate dehydrogenase A], PDK4 [pyruvate dehydrogenase kinase 4], SDH [succinate dehydrogenase], CPT1b [carnitine palmitoyl transferase 1b], or HMGCS2 [3-hydroxy-3-methylglutaryl-CoA synthase 2] is sufficient to partially reverse metabolic reprogramming and promotes adult cardiomyocyte proliferation. How metabolic reprogramming regulates cardiomyocyte proliferation is not clearly defined. The possible mechanisms involve biosynthetic pathways from the glycolysis shunts and the epigenetic regulation induced by metabolic intermediates. Metabolic manipulation could represent a new approach to stimulate cardiac regeneration; however, the efficacy of these manipulations requires optimization, and novel molecular targets need to be defined. In this review, we summarize the features, triggers, and molecular regulatory networks responsible for metabolic reprogramming and discuss the current understanding of metabolic reprogramming as a critical determinant of cardiomyocyte proliferation.

ZebraReg-a novel platform for discovering regulators of cardiac regeneration using zebrafish.

Cardiovascular disease is the leading cause of death worldwide with myocardial infarction being the most prevalent. Currently, no cure is available to either prevent or revert the massive death of cardiomyocytes that occurs after a myocardial infarction. Adult mammalian hearts display a limited regeneration capacity, but it is insufficient to allow complete myocardial recovery. In contrast, the injured zebrafish heart muscle regenerates efficiently through robust proliferation of pre-existing myocardial cells. Thus, zebrafish allows its exploitation for studying the genetic programs behind cardiac regeneration, which may be present, albeit dormant, in the adult human heart. To this end, we have established ZebraReg, a novel and versatile automated platform for studying heart regeneration kinetics after the specific ablation of cardiomyocytes in zebrafish larvae. In combination with automated heart imaging, the platform can be integrated with genetic or pharmacological approaches and used for medium-throughput screening of presumed modulators of heart regeneration. We demonstrate the versatility of the platform by identifying both anti- and pro-regenerative effects of genes and drugs. In conclusion, we present a tool which may be utilised to streamline the process of target validation of novel gene regulators of regeneration, and the discovery of new drug therapies to regenerate the heart after myocardial infarction.

Progresses and perspectives on natural polysaccharide based hydrogels for repair of infarcted myocardium

Myocardial infarction (MI) is serious health threat and impairs the quality of life. It is a major causative factor of morbidity and mortality. MI leads to the necrosis of cardio-myocytes, cardiac remodelling and dysfunction, eventually leading to heart failure. The limitations of conventional therapeutic and surgical interventions and lack of heart donors have necessitated the evolution of alternate treatment approaches for MI. Polysaccharide hydrogel based repair of infarcted myocardium have surfaced as viable option for MI treatment. Polysaccharide hydrogels may be injectable hydrogels or cardiac patches. Injectable hydrogels can in situ deliver cells and bio-actives, facilitating in situ cardiac regeneration and repair. Polysaccharide hydrogel cardiac patches reduce cardiac wall stress, and inhibit ventricular expansion and promote angiogenesis. Herein, we discuss about MI pathophysiology and myocardial microenvironment and how polysaccharide hydrogels are designed to mimic and support the microenvironment for cardiac repair. We also put forward the versatility of the different polysaccharide hydrogels in mimicking diverse cardiac properties, and acting as a medium for delivery of cells, and therapeutics for promoting angiogenesis and cardiac repair. The objectives of this review is to summarize the factors leading to MI and to put forward how polysaccharide based hydrogels promote cardiac repair. This review is written to enable researchers understand the factors promoting MI so that they can undertake and design novel hydrogels for cardiac regeneration.