Electrospun nanofiber is one of the promising alternatives for use in tissue engineering and drug delivery due to its controllable characteristics. However, choosing an appropriate biomaterial for a specific tissue regeneration plays a significant role in fabricating functional tissue-engineered constructs. Heart extracellular matrix (ECM)-derived electrospun nanofiber which mimic the physicochemical and structural characteristics of cardiac tissue is advantageous for cardiac tissue engineering. In this study, acellular calf heart ECM has been investigated as a potential biomaterial to be electrospun in a novel combination with poly vinyl pyrrolidone (PVP), gelatin (Gel) and polycaprolactone (PCL) for cardiac tissue engineering. The obtained fibers were aligned, uniform, and bead free. After fabrication, the scaffolds were cross-linked in glutaraldehyde vapor to become mechanically stronger and dissoluble in the aqueous environments. Considering surface topography, biocompatibility, hydrophilicity, and mechanical properties, the fabricated hybrid electrospun ECM/PVP/Gel/PCL fibers can be proposed as a biomimetic scaffold for heart tissue engineering applications.

Heart failure (HF) is one of the most important cardiovascular diseases (CVD), causing many die every year. Cardiac tissue engineering is a multidisciplinary field for creating functional tissues to improve the cardiac function of the damaged heart and get hope for end-stage patients. Recent works have focused on creating engineered cardiac tissue ex-vivo. Simultaneously, new approaches are used to study ways of induction of regeneration in the damaged heart after injury. The heart as a complex physiological pump consists of many cells such as cardiomyocytes (80–90% of the heart volume). These cardiomyocytes are elongated, aligned, and have beating properties. To create the heart muscle, which should be functional, soft and elastic scaffolds are required to resemble the native heart tissue. These mechanical characteristics are not compatible with all materials and should be well selected. Some scaffolds promote the viability and differentiation of stem cells. Each material has advantages and disadvantages with relevant influence behavior for cells. In this review, we present an overview of the general approaches developed to generate functional cardiac tissues, discussing the different cell sources, biomaterials, pharmacological agents, and engineering strategies in this manner. Moreover, we discuss the main challenges in cardiac tissue engineering that cause difficulties to construct heart muscle. We trust that researchers interested in developing cardiac tissue engineering will find the information reviewed here useful. Furthermore, we think that providing a unified framework will further the development of human engineered cardiac tissue constructs.

Heart failure is one of the leading causes of death worldwide. End stage disease often requires heart transplantation, which is hampered by donor organ shortage. Tissue engineering represents a promising alternative approach for cardiac repair. For the generation of artificial heart muscle tissue several cell types, scaffold materials and bioreactor designs are under investigation. In this review, the use of mesenchymal stem cells derived from human umbilical cord tissue (UCMSC) for cardiac tissue engineering will be discussed.

Because of the ability of stem cells to self-renew and differentiate into cardiomyocytes, they are optimal cell sources for cardiac tissue engineering. Since heart cells experience cyclic strain and pulsatile flow in vivo, these mechanical stimuli are essential factors for stem cell differentiation. This study aimed to investigate the effect of a combination of pulsatile flow and cyclic strain on the shear stress created on the embryonic stem cell layer with a elastic property in a perfusion bioreactor by using the fluid-solid interaction (FSI) method. In this study, the frequency and stress phase angle had been assumed as a variable. The results show that the maximum shear stress at frequencies of 0.33, and 1 Hz and with frequency differences in cyclic strain (0.33 Hz) and pulsatile flow (1 Hz) are 0.00562, 0.02, and 0.01 dyn/cm², respectively. Moreover, in the stress phase angles 0, , and , the maximum shear stress are equal to 0.00562, 0.009, and 0.014 dyn/cm², respectively. The results of this study can be an effective step in developing cardiac tissue engineering and a better understanding of the effects of mechanical stimuli on stem cell differentiation.

Cardiovascular diseases (CVDs) are the most prevalent cause of fatalities worldwide, affecting both cardiac and vascular tissues. Tissue engineering is a promising treatment alternative for people with end-stage CVDs; however, it has disadvantages such as poor scaffold design control and insufficient vascularization. 3D bioprinting, a recent advancement, has overcome these restrictions by creating layer-by-layer structures such as organs, scaffolds, and blood vessels. This method enables precise control over cell distribution, architectural structure, and compositional correction. Furthermore, since cardiac tissue is electroactive, incorporating electroconductive nanomaterials into the scaffold facilitates intracellular communication, mimics the heart's biochemical and biomechanical microenvironment, and prevents arrhythmia in the heart. In addition, these electroconductive materials can improve the quality of 3D-printed scaffolds. In this study, we will review the different techniques of 3D printing hydrogels after evaluating the many types of hydrogels employed for cardiac tissue engineering (CTE). Then, we will discuss the influence of incorporating electroconductive fillers into hydrogels on printed scaffold quality. Finally, we will briefly discuss the challenges and potentials.

Biomaterials currently utilized for the regeneration of myocardial tissue seem to associate with certain restrictions, including deficiency of electrical conductivity and sufficient mechanical strength. These two factors play an important role in cardiac tissue engineering and regeneration. The contractile property of cardiomyocytes depends on directed signal transmission over the electroconductive systems that happen inside the innate myocardium. Because of their distinctive electrical behavior, electroactive materials such as graphene might be used for the regeneration of cardiac tissue.

In this review, we aim to provide deep insight into the applications of graphene and graphene derivative-based hybrid polymeric scaffolds in cardiomyogenic differentiation and cardiac tissue regeneration.

Synthetic biodegradable polymers are considered as a platform because their degradation can be controlled over time and easily functionalized. Therefore, graphene-polymeric hybrid scaffolds with anisotropic electrical behavior can be utilized to produce organizational and efficient constructs for macroscopic cardiac tissue engineering. In cardiac tissue regeneration, natural polymer based-scaffolds such as chitosan, gelatin, and cellulose can provide a permissive setting significantly supporting the differentiation and growth of the human induced pluripotent stem cells -derived cardiomyocytes, in large part due to their negligible immunogenicity and suitable biodegradability.

Cardiac tissue regeneration characteristically utilizes an extracellular matrix (scaffold), cells, and growth factors that enhance cell adhesion, growth, and cardiogenic differentiation. From the various evaluated electroactive polymeric scaffolds for cardiac tissue regeneration in the past decade, graphene and its derivatives-based materials can be utilized efficiently for cardiac tissue engineering.

A cardiac infarction is the leading cause of death worldwide. Although the common treatments, including medication and various grafts, are unable to return the patients to their normal life, a cardiac patch is a promising technique in the field of tissue engineering that can stimulate the natural regeneration process of the diseased tissue via a scaffold with appropriate mechanical properties, biocompatibility and electrical conductivity. In this study, the composite scaffolds based on alginate (ALG) were fabricated through freeze-drying and coated with different concentrations of graphene oxide (GO) to make ALG/xGO (x=0.01, 0.05 and 0.1 wt. %) scaffolds. The scaffolds were characterized in terms of morphology, physicochemical structure, tensile strength, electrical conductivity, and cell response and gene expression. The presence of GO provided interconnected pores in the composite scaffolds. Adding GO up to 0.1 wt.% significantly enhanced Young’s modulus up to 5.5 MPa and electrical conductivity up to 8.59 S.m-1 (p≤0.05). Additionally, GO improved the vitality of human umbilical vein endothelial cells (HUVECs) compared to the scaffold without GO.  Investigating cell attachment of L929 fibroblasts indicated that the optimal content of GO at 0.05 wt.% can provide better places for cellular nesting due to the appropriate size of pores for cell/material interactions. The increase in the amount of GO up to 0.1 wt.% lead to a significant increase in gene expression of VEGFR-2 compared to the other scaffolds and tissue culture plate. We found that the prepared ALG/0.1GO composite scaffold could be appropriate for further experiments on cardiac tissue engineering applications.

This work introduces the novel gelatin/chitosan blend scaffolds containing different amounts of functionalized multi-walled carbon nanotubes (f-MWCNTs) up to 0.1wt%, which were prepared by freeze drying (freezing and lyophilization). The composite scaffolds were characterized by Fourier transformed infrared spectroscopy (FTIR) to distinguish the functional groups and different bonds in the structure of composite, and field-emission scanning electron microscope (FE−SEM) to evaluate the morphology of scaffolds. The scaffolds with the porosity of 89−93% and pore size of 40−200µm could be obtained by freezing at −20 °C and subsequent lyophilization. The porosity and swelling ratio of scaffolds were decreased, but the pore diameter was increased with an addition of f-MWCNTs. The electrical conductivity of incorporated scaffolds showed a significant increase with f-MWCNTs at an amount of 0.05wt%, and could achieve to those of the heart muscle. Compressive mechanical properties of the scaffolds revealed that the incorporation of f-MWCNTs led to significantly stiff the biopolymeric scaffold. The findings indicate that these novel fabricated composite scaffolds have microstructurally and electrically the potential to use in cardiac tissue engineering applications.

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.