Myocardium tissue is an electroactive tissue capable of transferring electrical signals, which lead to synchronized beating of heart. Electrical impulses originate from sinoatrial node and spread though myocardium to induce mechanical contraction of cardiomyocytes. As the leading cause of death, worldwide, cardiovascular diseases are often accompanied by disruption of electrical integrity of cardiac tissue and arrhythmia. In many arrhythmias, lack of conduction as well as unidirectional conduction result in insufficient intercellular electrical coupling at gap junctions. Due to limitation of conventional treatment methods such as heart transplantation, pathological and therapeutic researches in cardiac electrical disorders have increased in last few years. The aim of this study was to review the last studies in electrical system of heart and its disorder along with the results and the future of the cardiovascular tissue therapy method based on Conductive biomaterial.
Electrical integrity is essential for normal functioning of the heart. Among the new methods of treating heart failure and improving the electrical integrity of the disorder caused by these defects, tissue engineering with the use of conductive electrical conductive materials has been widely considered along with other methods. Three main types of conductive materials have been used for tissue engineering application: (1) Gold-based materials (2) Carbon-based materials (3) Conductive polymers.

In the recent years, bioengineered cardiac tissues are of particular significance because of the extremely limited ability of the myocardium to self-regenerate. In this article, the recent advancements in the development of experimental in vitro platforms for next generation of the diagnostics and therapy validation are reviewed. Specially, here the present progress of the microfluidics technology application such as micro/nano fibers, micropatterning, and 3D bioprinting with sacrificial material or with microfluidic channels for the development of cardiovascular systems’ biofabrication at the tissue- and organ levels is described. With all the improvements in this field, there are still difficulties in prolonged cells viability, thick tissue fabrication for higher mimicry levels, and scaffolds mechanical stability in vivo. Until now, microfluidic methods pave the way for in vitro recapitulating of cardiovascular tissue for drug testing and providing basic knowledge of organ’s functions. In the future, with novel microphysiological systems, the transition from bench to bedside will be accelerated.

Adipose-derived stem cells (ADSCs) represent a promising source of cells for cardiac tissue engineering and repair of the injured heart. However, better understanding of the factors affecting the cardiac differentiation of ADSCs is required before clinical application of these cells. Current study was designed to investigate the role of bFGF and BMP4 in cardiac differentiation of human ADSCs.
ADSCs were isolated from human abdominal subcutaneous adipose tissue and cultured. For cardiac differentiation, ADSCs were treated with 10 ng/ml bFGF and 20, 50 or 100 ng/ml BMP4 in a medium containing 10% FBS or 0.5% B27 for four days. Then the induction factors were completely omitted, and the cells were maintained in 10% FBS-containing medium for up to three weeks. At the end of differentiation period, the expression of some cardiac markers was assessed by RT-PCR, qPCR and immunocytochemistry.
The differentiated ADSCs expressed cardiac-specific genes. Based on qPCR analysis, the maximum expression level of ANF and MLC2A mRNAs was detected in the cells treated with 10 ng/ml bFGF and 20 ng/ml BMP4 in the FBS-containing medium. Moreover, FBS supplementation of induction medium was more effective than the B27-containing medium for cardiac differentiation of ADSCs by bFGF and BMP4. The cells treated with 10 ng/ml bFGF and 20 ng/ml BMP4 in FBS-containing medium expressed cardiac troponin I and α-actinin proteins.
It seems that a combination of bFGF and BMP4 improves cardiac differentiation of ADSCs. Moreover, bFGF and BMP4 are more effective for cardiac differentiation when the induction medium is supplemented with FBS than B27. This may be due to the presence of insulin in B27 supplement.

Injectable hydrogels that mimic heart tissues can be considered a promissing perspective towards the future developments of cardiac tissue engineering. This study aims to fabricate an injectable, thermosensitive hydrogel consisting of chitosan/gelatin/glycerol phosphate. Due to their unique electro-conductivity characteristic, hydrogels can provide a suitable environment to accelerate cardiac cell proliferation. Polyaniline/multi-walled carboxylated carbon nanotube (PAni/c-MWNT) was prepared using Sodium Dodecyl Sulfate (SDS) emulsion. To prevent the interaction between the PAni/c-MWNT nanocomposite and hydrogel, the nanocomposite was coated with gelatin to form polyaniline/carboxylated carbon nanotube/gelatin (PAni/c-MWNT/G). The PAni/c-MWNT/G nanocomposite was then dispersed to provide electrical signals throughout the hydrogel. The gelation time, gel temperature, and mechanical properties of the hydrogel were measured using a rheometer. FTIR spectroscopy results revealed that the interaction between the aniline and c-MWNT/G could change the position of the quinone and benzene peaks. The conductivity of hydrogel-containing nanocomposite was found to be higher than that of c-MWNT and PAni. Scanning Electron Microscopy (SEM) confirmed the uniform distribution of PAni/c-MWNT/G nanocomposite throughout the hydrogel. The degradation rate of conductive hydrogel is lower than that of pure hydrogel. The MTT assay test showed the biocompatibility of the cell-hydrogel. Finally, Mesenchymal Stem Cells (MSCs) were cultured in the hydrogels for 14 days. Cell adhesion, cell viability, and proliferation were also examined. This study utilized PAni/c-MWNT/G, for the first time, to enhance the electro-conductivity of chitosan/gelatin/glycerol phosphate hydrogel. This conductive thermosensitive injectable hydrogel can be used to regenerate cardiac tissue and other electroactive tissues.

 This research, design and fabrication of a composite scaffold for growth, proliferation and differentiation of Cardiac Progenitor Cells (CPCs) has been considered.

 Polycaprolactone / Gelatin composite scaffolds with a ratio of 70:30 and with the most similarities to the cardiac extracellular matrix was fabricated with aligned nanofibers. Using scanning electron microscopy (SEM), mechanical strength analysisand also contact angel test, the scaffold was investigated due to have the most necessary characteristics to be proportional for cardiac scaffold. Finally, By Real time-PCR test, the expression of the specific genes related to the Cardiac Progenitor Cells differentiation (MYH-6, TTN and CX-43) has been analyzed.

 Based on our results from contact angle test and mechanical strength experiments, we concluded that our designed scaffold is suitable for the culture of Cardiac Progenitor Cells on it. The Real time-PCR analysis also showed the good expression of genes associated with contraction.

 What makes the cardiomyocytes different from other cells is their contraction related to specific cardiac genes being responsible for beating synchronization. The results of this study showed that aligned Polycaprolactone / Gelatin composite scaffold has the appropriate potential for induction of cardiac progenitor cells differentiation and application in heart tissue engineering.

The direct approach of cardiac tissue engineering is to mimic the natural tissue of heart, considering the significant role of scaffolding and mechanical simulation. 

To achieve this purpose, a composite Polycaprolactone (PCL)/Gelatin electrospun scaffold with a ratio of 70:30 and with the most similarities to the cardiac extracellular matrix was fabricated with aligned nanofibers. The scaffold was evaluated using scanning electron microscopy (SEM), mechanical strength analysis, and contact angle test. To simulate the cardiac contraction, a developed Mechanical Loading Device (Bioreactor) was designed to apply a mechanical load with a specific frequency and tensile rate values in the direction of aligned nanofibers due to simulating natural cardiac tissue.

Based on our results from the contact angle and mechanical strength tests, we concluded that our designed scaffold has appropriate adhesion and strength to use as cardiac scaffold and is suitable for imposing the frequency of 1Hz and 10% strain. The Bioreactor also worked properly in producing the required frequency, tensile rate and temperature. 

Since an essential difference between cardiomyocytes and other cells is their contraction, manufacturing a biomimetic bioreactor to simulate the normal cardiac contraction of cardiomyocytes and their required temperature to be survived in-vitro could be a promising approach in cardiac tissue engineering.

In spite of promising results of conventional treatments for myocardial infarction, including medications, stent implantation, and coronary artery bypass grafting, the disease and its complications, especially heart failure, are highly prevalent because these methods could not reverse the cell loss, which is the main problem. Currently, heart transplantation, as the last option for treatment of heart failure, has major limitations including the low number of appropriate donors and underlying diseases in recipients. The present study is presented as a review paper. Using related keywords, including myocardial infarction, cell therapy, stem cell, cardiac tissue engineering, and clinical trials, studies published up to 2018 were collected from reliable databases, including Google Scholar, PubMed, Scopus, and Elsevier. Among potential candidates, those which were the most relevant to the purposes of the study were selected and evaluated. The stem cells application for regeneration of damaged tissues is one of the great researchers’ achievements. In spite of various scientific, legal, and ethical concerns, several companies target stem cells transplantation for cardiac diseases in commercial way. There are many in situ, in vitro, and cell-loaded scaffold and cell sheet engineering studies in tissue engineering field. Despite the promising results of stem cells application, many challenges still lay ahead of this pathway including optimal cell, dosage, time and route administration selection, and the immune response modulations. Currently, extensive research is ongoing. In this regard, the successful results of various clinical trials made by different companies and health centers have led to commercialization of products. Some of them are addressed in the current review article. However, more research is needed to clarify the efficacy of these studies.

Myocardial infarction is one of the leading causes of death worldwide. The rate of heart tissue regeneration is limited following myocardial infarction. The combination of cell therapy and tissue engineering technology can lead to widespread clinical applications. In this study, we investigated the capability of the scaffolds to support cardiomyocyte attachment and growth cardiac tissue engineering.

A bacterial cellulose (BC) scaffold was prepared and coated with gelatin to form a gelatin-coated BC (BCG) scaffold. BC and BCG scaffolds were characterized using SEM, FE-SEM, AFM, and contact angle measurements. Neonatal rat-ventricular cardiomyocytes (nr-vCMCs) were cultured on scaffolds to explore the capability of the scaffolds (for cell attachment and survival) and were compared with human dermal fibroblasts (HDFs)

The results showed that the average diameter of nanofibrils and surface roughness were suitable for cardiomyocyte culture. The contractile activity of nr-vCMCs remained during culture duration, but the mean beating frequency gradually decreased from the fifth to seventh day of   culture. According to the results of light microscopy images, the adhesion of HDFs on the scaffolds was greater than cardiomyocyte attachment throughout the cell culture duration.

In addition to not being cytotoxic, BC and BCG have the appropriate physicochemical properties to preserve the morphology and contractile function of neonatal rat cardiomyocytes.

.The artery diseases such as the coronary arteries are of the important cardiovascular diseases. The autograft as a common surgical is the main treatment for this problem, but in many patients, the autografts are not. So, due to a large number of requirements, it needs to find suitable replacements for diseases of blood vessels. Tissue engineering at the nanoscale level is a promising approach to the design and fabrication of artificial blood vessels. Nanomaterial structures are highly contributive in tissue engineering vascular scaffolds (TEVS) due to their ability in mimicking the nanoscale dimension of the natural extracellular matrix (ECM) and the existing mechanical match between the native vessel and the scaffold. The aim of this research was developing and mechanically improving nano-fibrous composite scaffolds using blend electrospinning methods with different ratios of the polyethylene terephthalate (PET), polyurethane (PU) and polycaprolactone (PCL). The morphological and mechanical properties all structures were evaluated using SEM, FTIR and tensile properties. The neat and composite structures were completely intact with randomly oriented fibers and without any beads. Results showed that the average fiber diameter, porosity, stress and Young’s modulus changes’ range in composite structures (PCL/PU and PET/PU) obtained 343 ± 94 to 382 ± 83 nm, 58.6 ± 3.12 to 81 ± 1.7 %, 2.66 ± 0.39 to 19.05 ± 3.2 MPa and 3.18 ± 0.09 to 41.4± 3.31 MPa, respectively. The fabricated scaffolds and especially PET/PU structure exhibited suitable mechanical and biological properties and clinical requirements as a small-diameter vascular graft.