Developing a biomimetic platform that can effectively support myocardial repair and regeneration after a heart attack remains a major challenge for researchers. Polyurethanes (PU), known for their versatile properties, are increasingly being recognized as promising materials for creating cardiac patches. This research study developed the synthesis of a novel unsaturated chain extender via the Baylis-Hillman reaction for incorporation into the backbone of PU to create the unsaturated bridge for post-modification response. Thiol-ene chemistry performed post-modification of unsaturated hard domains of PU with thiolated gelatin as another reactant. Modification of the hard segment domains of PU with gelatin can have a synergistic effect on fabricating a new platform for repairing cardiac tissue. The films were characterized by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Nuclear Magnetic Resonance (NMR), mechanical tests, in vitro degradation rate, water contact angle measurement, and swelling measurement. Metabolic activity and cytocompatibility of the cells onto the films were assessed by MTT assay. An investigation of cardiac-specific marker expression was conducted using immunofluorescence staining and quantitative real-time PCR. The findings showed that none of the substances were cytotoxic to cardiomyocytes, and that the expression of cadiac-specific genes, such as Troponin T, GATA4, Connexin43, and Alpha-SMA, was higher than that of the control group.

The development of conducting polymeric nanocomposites patches for cardiac tissue engineering has opened new possibilities for restoring the health of infarcted heart tissues. Herein, we report the fabrication of biocompatible and relatively cost-effective poly(vinyl alcohol)/alginate-based hydrogels patches modified with different conducting nanofillers such as silver nanoparticles, polyaniline nanofibers, copper oxide nanoleaves, and graphene oxide nanosheets. The impact of the different nanofiller materials on the molecular structure, charge transport mechanism and mechanical characteristics of the designed nanocomposites patches was investigated. In addition, some significant parameters of the nanocomposites were characterized such as swelling ability, antioxidant activity as well as hemocompatibility. Infrared spectroscopy results demonstrated the occurrence of different interactions between the included nanofillers and the polymer matrix depending on the type of the nanofiller. Moreover, conductivity measurements revealed that only the polyaniline nanofibers-modified nanocomposites hydrogels showed the highest conductivity compared to other counterparts. Mechanical characterization, antioxidant activity, swelling and hemocompatibility proved the suitability of the developed polyaniline nanofibers-modified nanocomposites hydrogels as potential candidates for successful application in cardiac tissue engineering.

This comprehensive review offers a thorough examination of fetal heart rate (fHR) monitoring methods, which are an essential component of prenatal care for assessing fetal health and identifying possible problems early on. It examines the clinical uses, accuracy, and limitations of both modern and traditional monitoring techniques, such as electrocardiography (ECG), ballistocardiography (BCG), phonocardiography (PCG), and cardiotocography (CTG), in a variety of obstetric scenarios. A particular focus is on the most recent developments in textile-based wearables for fHR monitoring. These innovative devices mark a substantial advancement in the field and are noteworthy for their continuous data collection capability and ergonomic design. The review delves into the obstacles that arise when incorporating these wearables into clinical practice. These challenges include problems with signal quality, user compliance, and data interpretation. Additionally, it looks at how these technologies could improve fetal health surveillance by providing expectant mothers with more individualized and non-intrusive options, which could change the prenatal monitoring landscape.

Finding novel treatments for cardiovascular diseases (CVDs) is a hot topic in medicine; cell-based therapies have reported promising news for controlling dangerous complications of heart disease such as myocardial infarction (MI) and heart failure (HF). Various progenitor/stem cells were tested in various in-vivo, in-vitro, and clinical studies for regeneration or repairing the injured tissue in the myocardial to accelerate the healing. Fetal, adult, embryonic, and induced pluripotent stem cells (iPSC) have revealed the proper potency for cardiac tissue repair. As an essential communicator among cells, exosomes with specific contacts (proteins, lncRNAs, and miRNAs) greatly promote cardiac rehabilitation. Interestingly, stem cell-derived exosomes have more efficiency than stem cell transplantation. Therefore, stem cells induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), cardiac stem cells (CDC), and skeletal myoblasts) and their-derived exosomes will probably be considered an alternative therapy for CVDs remedy. In addition, stem cell-derived exosomes have been used in the diagnosis/prognosis of heart diseases. In this review, we explained the advances of stem cells/exosome-based treatment, their beneficial effects, and underlying mechanisms, which will present new insights in the clinical field in the future.

Cardiovascular diseases (CDs) are the foremost cause of death worldwide. Several promising therapeutic methods have been developed for this approach, including pharmacological, surgical intervention, cell therapy, or biomaterial implantation since heart tissue is incapable of regenerating and healing on its own. The best treatment for heart failure to date is heart transplantation and invasive surgical intervention, despite their invasiveness, donor limitations, and the possibility of being rejected by the patient's immune system. To address these challenges, research is being conducted on less invasive and efficient methods. Consequently, graphene-based materials (GBMs) have attracted a great deal of interest in the last decade because of their exceptional mechanical, electrical, chemical, antibacterial, and biocompatibility properties. An overview of GBMs' applications in the cardiovascular system has been presented in this article. Following a brief explanation of graphene and its derivatives' properties, the potential of GBMs to improve and restore cardiovascular system function by using them as cardiac tissue engineering, stents, vascular bypass grafts,and heart valve has been discussed.

The aim of this study is to provide an overview of the current state-of-the-art in the fabrication of bioceramic scaffolds for bone tissue engineering, with an emphasis on the use of three-dimensional (3D) technologies coupled with generative design principles. The field of modern medicine has witnessed remarkable advancements and continuous innovation in recent decades, driven by a relentless desire to improve patient outcomes and quality of life. Central to this progress is the field of tissue engineering, which holds immense promise for regenerative medicine applications. Scaffolds are integral to tissue engineering and serve as 3D frameworks that support cell attachment, proliferation, and differentiation. A wide array of materials has been explored for the fabrication of scaffolds, including bioceramics (i.e., hydroxyapatite, beta-tricalcium phosphate, bioglasses) and bioceramic-polymer composites, each offering unique properties and functionalities tailored to specific applications. Several fabrication methods, such as thermal-induced phase separation, electrospinning, freeze-drying, gas foaming, particle leaching/solvent casting, fused deposition modeling, 3D printing, stereolithography and selective laser sintering, will be introduced and thoroughly analyzed and discussed from the point of view of their unique characteristics, which have proven invaluable for obtaining bioceramic scaffolds. Moreover, by highlighting the important role of generative design in scaffold optimization, this review seeks to pave the way for the development of innovative strategies and personalized solutions to address significant gaps in the current literature, mainly related to complex bone defects in bone tissue engineering.

Current clinically used electronic implants, including cardiac pacing leads for epicardial monitoring and stimulation of the heart, rely on surgical suturing or direct insertion of electrodes to the heart tissue. These approaches can cause tissue trauma during the implantation and retrieval of the pacing leads, with the potential for bleeding, tissue damage, and device failure. Here, we report a bioadhesive pacing lead that can directly interface with cardiac tissue through physical and covalent interactions to support minimally invasive adhesive implantation and gentle on-demand removal of the device with a detachment solution. We developed 3D-printable bioadhesive materials for customized fabrication of the device by graft-polymerizing polyacrylic acid on hydrophilic polyurethane and mixing with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) to obtain electrical conductivity. The bioadhesive construct exhibited mechanical properties similar to cardiac tissue and strong tissue adhesion, supporting stable electrical interfacing. Infusion of a detachment solution to cleave physical and covalent cross-links between the adhesive interface and the tissue allowed retrieval of the bioadhesive pacing leads in rat and porcine models without apparent tissue damage. Continuous and reliable cardiac monitoring and pacing of rodent and porcine hearts were demonstrated for 2 weeks with consistent capture threshold and sensing amplitude, in contrast to a commercially available alternative. Pacing and continuous telemetric monitoring were achieved in a porcine model. These findings may offer a promising platform for adhesive bioelectronic devices for cardiac monitoring and treatment.

In tissue engineering, 3D printing represents a versatile technology employing inks to construct three-dimensional living structures, mimicking natural biological systems. This technology efficiently translates digital blueprints into highly reproducible 3D objects. Recent advances have expanded 3D printing applications, allowing for the fabrication of diverse anatomical components, including engineered functional tissues and organs. The development of printable inks, which incorporate macromolecules, enzymes, cells, and growth factors, is advancing with the aim of restoring damaged tissues and organs. Polysaccharides, recognized for their intrinsic resemblance to components of the extracellular matrix have garnered significant attention in the field of tissue engineering. This review explores diverse 3D printing techniques, outlining distinctive features that should characterize scaffolds used as ideal matrices in tissue engineering. A detailed investigation into the properties and roles of polysaccharides in tissue engineering is highlighted. The review also culminates in a profound exploration of 3D polysaccharide-based hydrogel applications, focusing on recent breakthroughs in regenerating different tissues such as skin, bone, cartilage, heart, nerve, vasculature, and skeletal muscle. It further addresses challenges and prospective directions in 3D printing hydrogels based on polysaccharides, paving the way for innovative research to fabricate functional tissues, enhancing patient care, and improving quality of life.

Cardiovascular diseases, particularly myocardial infarction (MI), are the leading cause of death worldwide and a major contributor to disability. Cardiac tissue engineering is a promising approach for preventing functional damage or improving cardiac function after MI. We aimed to introduce a novel electroactive cardiac patch based on reduced graphene oxide-coated alginate scaffolds due to the promising functional behavior of electroactive biomaterials to regulate cell proliferation, biocompatibility, and signal transition.

The fabrication of novel electroactive cardiac patches based on alginate (ALG) coated with different concentrations of reduced graphene oxide (rGO) using sodium hydrosulfite is described here. The prepared scaffolds were thoroughly tested for their physicochemical properties and cytocompatibility. ALG-rGO scaffolds were also tested for their antimicrobial and antioxidant properties. Subcutaneous implantation in mice was used to evaluate the scaffolds' ability to induce angiogenesis.

The Young modulus of the scaffolds was increased by increasing the rGO concentration from 92 ± 4.51 kPa for ALG to 431 ± 4.89 kPa for ALG-rGO-4 (ALG coated with 0.3% w/v rGO). The scaffolds' tensile strength trended similarly. The electrical conductivity of coated scaffolds was calculated in the semi-conductive range (~ 10-4 S/m). Furthermore, when compared to ALG scaffolds, human umbilical vein endothelial cells (HUVECs) cultured on ALG-rGO scaffolds demonstrated improved cell viability and adhesion. Upregulation of VEGFR2 expression at both the mRNA and protein levels confirmed that rGO coating significantly boosted the angiogenic capability of ALG against HUVECs. OD620 assay and FE-SEM observation demonstrated the antibacterial properties of electroactive scaffolds against Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes. We also showed that the prepared samples possessed antioxidant activity using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and UV-vis spectroscopy. Histological evaluations confirmed the enhanced vascularization properties of coated samples after subcutaneous implantation.

Our findings suggest that ALG-rGO is a promising scaffold for accelerating the repair of damaged heart tissue.

Cardiovascular diseases are the primary cause of death worldwide. Despite significant advances in pharmacological treatments and surgical interventions to restore heart function after myocardial infarction, it can progress to heart failure due to the restricted inherent potential of adult cardiomyocytes to self-regenerate. Hence, the evolution of new therapeutic methods is critical. Nowadays, novel approaches in tissue engineering have assisted in restoring biological and physical specifications of the injured myocardium and, hence, cardiac function. The incorporation of a supporting matrix that could mechanically and electronically support the heart tissue and stimulate the cells to proliferate and regenerate will be advantageous. Electroconductive nanomaterials can facilitate intracellular communication and aid synchronous contraction via electroactive substrate creation, preventing the issue of arrhythmia in the heart. Among a wide range of electroconductive materials, graphene-based nanomaterials (GBNs) are promising for cardiac tissue engineering (CTE) due to their outstanding features including high mechanical strength, angiogenesis, antibacterial and antioxidant properties, low cost, and scalable fabrication. In the present review, we discuss the effect of applying GBNs on angiogenesis, proliferation, and differentiation of implanted stem cells, their antibacterial and antioxidant properties, and their role in improving the electrical and mechanical properties of the scaffolds for CTE. Also, we summarize the recent research that has applied GBNs in CTE. Finally, we present a concise discussion on the challenges and prospects.

Medical soft robotics constitutes a rapidly developing field in the treatment of cardiovascular diseases, with a promising future for millions of patients suffering from heart failure worldwide. Herein, the present state and future direction of artificial muscle-based soft robotic biomedical devices in supporting the inotropic function of the heart are reviewed, focusing on the emerging electrothermally artificial heart muscles (AHMs). Artificial muscle powered soft robotic devices can mimic the action of complex biological systems such as heart compression and twisting. These artificial muscles possess the ability to undergo complex deformations, aiding cardiac function while maintaining a limited weight and use of space. Two very promising candidates for artificial muscles are electrothermally actuated AHMs and biohybrid actuators using living cells or tissue embedded with artificial structures. Electrothermally actuated AHMs have demonstrated superior force generation while creating the prospect for fully soft robotic actuated ventricular assist devices. This review will critically analyze the limitations of currently available devices and discuss opportunities and directions for future research. Last, the properties of the cardiac muscle are reviewed and compared with those of different materials suitable for mechanical cardiac compression.

It is widely acknowledged that cardiovascular diseases (CVDs) continue to be the leading cause of death globally. Furthermore, CVDs are the leading cause of diminished quality of life for patients, frequently as a result of their progressive deterioration. Medical implants that release drugs into the body are active implants that do more than just provide mechanical support; they also have a therapeutic role. Primarily, this is achieved through the controlled release of active pharmaceutical ingredients (API) at the implementation site.

In this review, the authors discuss drug-eluting stents, drug-eluting vascular grafts, and drug-eluting cardiac patches with the aim of providing a broad overview of the three most common types of cardiac implant.

Drug eluting implants are an ideal alternative to traditional drug delivery because they allow for accurate drug release, local drug delivery to the target tissue, and minimise the adverse side effects associated with systemic administration. Despite the fact that there are still challenges that need to be addressed, the ever-evolving new technologies are making the fabrication of drug eluting implants a rewarding therapeutic endeavour with the possibility for even greater advances.

The conformation and self-assembly of four lipopeptides, peptide amphiphiles comprising peptides conjugated to lipid chains, in aqueous solution have been examined. The peptide sequence in all four lipopeptides contains the integrin cell adhesion RGDS motif, and the cytocompatibility of the lipopeptides is also analyzed. Lipopeptides have either tetradecyl (C₁₄, myristyl) or hexadecyl (C₁₆, palmitoyl) lipid chains and peptide sequence WGGRGDS or GGGRGDS, that is, with either a tryptophan-containing WGG or triglycine GGG tripeptide spacer between the bioactive peptide motif and the alkyl chain. All four lipopeptides self-assemble above a critical aggregation concentration (CAC), determined through several comparative methods using circular dichroism (CD) and fluorescence. Spectroscopic methods [CD and Fourier transform infrared (FTIR) spectroscopy] show the presence of β-sheet structures, consistent with the extended nanotape, helical ribbon, and nanotube structures observed by cryogenic transmission electron microscopy (cryo-TEM). The high-quality cryo-TEM images clearly show the coexistence of helically twisted ribbon and nanotube structures for C₁₄-WGGRGDS, which highlight the mechanism of nanotube formation by the closure of the ribbons. Small-angle X-ray scattering shows that the nanotapes comprise highly interdigitated peptide bilayers, which are also present in the walls of the nanotubes. Hydrogel formation was observed at sufficiently high concentrations or could be induced by a heat/cool protocol at lower concentrations. Birefringence due to nematic phase formation was observed for several of the lipopeptides, along with spontaneous flow alignment of the lyotropic liquid crystal structure in capillaries. Cell viability assays were performed using both L929 fibroblasts and C2C12 myoblasts to examine the potential uses of the lipopeptides in tissue engineering, with a specific focus on application to cultured (lab-grown) meat, based on myoblast cytocompatibility. Indeed, significantly higher cytocompatibility of myoblasts was observed for all four lipopeptides compared to that for fibroblasts, in particular at a lipopeptide concentration below the CAC. Cytocompatibility could also be improved using hydrogels as cell supports for fibroblasts or myoblasts. Our work highlights that precision control of peptide sequences using bulky aromatic residues within "linker sequences" along with alkyl chain selection can be used to tune the self-assembled nanostructure. In addition, the RGDS-based lipopeptides show promise as materials for tissue engineering, especially those of muscle precursor cells.

Cardiovascular diseases (CVDs) are known as the major cause of death worldwide. In spite of tremendous advancements in medical therapy, the gold standard for CVD treatment is still transplantation. Tissue engineering, on the other hand, has emerged as a pioneering field of study with promising results in tissue regeneration using cells, biological cues, and scaffolds. Three-dimensional (3D) bioprinting is a rapidly growing technique in tissue engineering because of its ability to create complex scaffold structures, encapsulate cells, and perform these tasks with precision. More recently, 3D bioprinting has made its debut in cardiac tissue engineering, and scientists are investigating this technique for development of new strategies for cardiac tissue regeneration. In this review, the fundamentals of cardiac tissue biology, available 3D bioprinting techniques and bioinks, and cells implemented for cardiac regeneration are briefly summarized and presented. Afterwards, the pioneering and state-of-the-art works that have utilized 3D bioprinting for cardiac tissue engineering are thoroughly reviewed. Finally, regulatory pathways and their contemporary limitations and challenges for clinical translation are discussed.

As the most prevalent structural protein in the extracellular matrix, collagen has been extensively investigated for biofabrication-based applications. However, its utilisation has been impeded due to a lack of sufficient mechanical toughness and the inability of the scaffold to mimic complex natural tissues. The anisotropic alignment of collagen fibres has been proven to be an effective method to enhance its overall mechanical properties and produce biomimetic scaffolds. This review introduces the complicated scenario of collagen structure, fibril arrangement, type, function, and in addition, distribution within the body for the enhancement of collagen-based scaffolds. We describe and compare existing approaches for the alignment of collagen with a sharper focus on electro-compaction. Additionally, various effective processes to further enhance electro-compacted collagen, such as crosslinking, the addition of filler materials, and post-alignment fabrication techniques, are discussed. Finally, current challenges and future directions for the electro-compaction of collagen are presented, providing guidance for the further development of collagenous scaffolds for bioengineering and nanotechnology.

Electrical conductivity is of great significance to cardiac tissue engineering and permits the use of electrical stimulation in mimicking cardiac pacing. The development of biomaterials for tissue engineering can incorporate physical properties that are uncommon to standard cell culture and can facilitate improved cardiomyocyte function. In this review, the PICOT question asks, "How has the application of external electrical stimulation in conductive scaffolds for tissue engineering affected cardiomyocyte behavior in in vitro cell culture?" The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, with predetermined inclusion and quality appraisal criteria, were used to assess publications from PubMed, Web of Science, and Scopus. Results revealed carbon nanotubes to be the most common conductive agent in biomaterials and rodent-sourced cell types as the most common cardiomyocytes used. To assess cardiomyocytes, immunofluorescence was used most often, utilizing proteins, such as connexin 43, cardiac α-actinin, and cardiac troponins. It was determined that the modal average stimulation protocol comprised 1-3 V square biphasic 50-ms pulses at 1 Hz, applied toward the end of cell culture. The addition of electrical stimulation to in vitro culture has exemplified it as a powerful tool for cardiac tissue engineering and brings researchers closer to creating optimal artificial cardiac tissue constructs.

Flow phantoms are used in experimental settings to aid in the simulation of blood flow. Custom geometries are available, but current phantom materials present issues with degradability and/or mimicking the mechanical properties of human tissue. In this study, a method of fabricating custom wall-less flow phantoms from a tissue-mimicking gel using 3D printed inserts is developed.

A 3D blood vessel geometry example of a bifurcated artery model was 3D printed in polyvinyl alcohol, embedded in tissue-mimicking gel, and subsequently dissolved to create a phantom. Uniaxial compression testing was performed to determine the Young's moduli of the five gel types. Angle-independent, ultrasound-based imaging modalities, Vector Flow Imaging (VFI) and Blood Speckle Imaging (BSI), were utilized for flow visualization of a straight channel phantom.

A wall-less phantom of the bifurcated artery was fabricated with minimal bubbles and continuous flow demonstrated. Additionally, flow was visualized through a straight channel phantom by VFI and BSI. The available gel types are suitable for mimicking a variety of tissue types, including cardiac tissue and blood vessels.

Custom, tissue-mimicking flow phantoms can be fabricated using the developed methodology and have potential for use in a variety of applications, including ultrasound-based imaging methods. This is the first reported use of BSI with an in vitro flow phantom.

Electrospinning is an innovative new fibre technology that aims to design and fabricate membranes suitable for a wide range of tissue engineering (TE) applications including vascular grafts, which is the main objective of this research work. This study dealt with fabricating and characterising bilayer structures comprised of an electrospun sheet made of polycaprolactone (PCL, inner layer) and an outer layer made of poly lactic-co-glycolic acid (PLGA) and a coaxial porous scaffold with a micrometre fibre structure was successfully produced. The membranes' propriety for intended biomedical applications was assessed by evaluating their morphological structure/physical properties and structural integrity when they underwent the degradation process. A scanning electron microscope (SEM) was used to assess changes in the electrospun scaffolds' structural morphology such as in their fibre diameter, pore size (μm) and the porosity of the scaffold surface which was measured with Image J software. During the 12-week degradation process at room temperature, most of the scaffolds showed a similar trend in their degradation rate except the 60 min scaffolds. The coaxial scaffold had significantly less mass loss than the bilayer PCL/PLGA scaffold with 1.348% and 18.3%, respectively. The mechanical properties of the fibrous membranes were measured and the coaxial scaffolds showed greater tensile strength and elongation at break (%) compared to the bilayer scaffolds. According to the results obtained in this study, it can be concluded that a scaffold made with a coaxial needle is more suitable for tissue engineering applications due to the improved quality and functionality of the resulting polymeric membrane compared to the basic electrospinning process. However, whilst fabricating a vascular graft is the main aim of this research work, the biological data will not present in this paper.

Myocardial infarction (MI), triggered by blockage of a coronary artery, remains the most common cause of death worldwide. After MI, the capability of providing sufficient blood and oxygen significantly decreases in the heart. This event leads to depletion of oxygen from cardiac tissue and consequently leads to massive cardiac cell death due to hypoxemia. Over the past few decades, many studies have been carried out to discover acceptable approaches to treat MI. However, very few have addressed the crucial role of efficient oxygen delivery to the injured heart. Thus, various strategies were developed to increase the delivery of oxygen to cardiac tissue and improve its function. Here, we have given an overall discussion of the oxygen delivery mechanisms and how the current technologies are employed to treat patients suffering from MI, including a comprehensive view on three major technical approaches such as oxygen therapy, hemoglobin-based oxygen carriers (HBOCs), and oxygen-releasing biomaterials (ORBs). Although oxygen therapy and HBOCs have shown promising results in several animal and clinical studies, they still have a few drawbacks which limit their effectiveness. More recent studies have investigated the efficacy of ORBs which may play a key role in the future of oxygenation of cardiac tissue. In addition, a summary of conducted studies under each approach and the remaining challenges of these methods are discussed.

Currentin vivoandin vitromodels fail to accurately recapitulate the human heart microenvironment for biomedical applications. This study explores the use of cardiac spheroids (CSs) to biofabricate advancedin vitromodels of the human heart. CSs were created from human cardiac myocytes, fibroblasts and endothelial cells (ECs), mixed within optimal alginate/gelatin hydrogels and then bioprinted on a microelectrode plate for drug testing. Bioprinted CSs maintained their structure and viability for at least 30 d after printing. Vascular endothelial growth factor (VEGF) promoted EC branching from CSs within hydrogels. Alginate/gelatin-based hydrogels enabled spheroids fusion, which was further facilitated by addition of VEGF. Bioprinted CSs contracted spontaneously and under stimulation, allowing to record contractile and electrical signals on the microelectrode plates for industrial applications. Taken together, our findings indicate that bioprinted CSs can be used to biofabricate human heart tissues for long termin vitrotesting. This has the potential to be used to study biochemical, physiological and pharmacological features of human heart tissue.

Cardiovascular disease is currently the top global cause of death, however, research into new therapies is in decline. Tissue engineering is a solution to this crisis and in combination with the use of carbon nanotubes (CNTs), which have drawn recent attention as a biomaterial, could facilitate the development of more dynamic and complex in vitro models. CNTs' electrical conductivity and dimensional similarity to cardiac extracellular proteins provide a unique opportunity to deliver scaffolds with stimuli that mimic the native cardiac microenvironment in vitro more effectively. This systematic review aims to evaluate the use and efficacy of CNTs for cardiac tissue scaffolds and was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Three databases were searched: PubMed, Scopus, and Web of Science. Papers resulting from these searches were then subjected to analysis against pre-determined inclusion and quality appraisal criteria. From 249 results, 27 manuscripts met the criteria and were included in this review. Neonatal rat cardiomyocytes were most commonly used in the experiments, with multi-walled CNTs being most common in tissue scaffolds. Immunofluorescence was the experimental technique most frequently used, which was employed for the staining of cardiac-specific proteins relating to contractile and electrophysiological function.

The induced pluripotent stem cells (iPSCs) are derived from somatic cells by using reprogramming factors such as Oct4, Sox2, Klf4, and c-Myc (OSKM) or Oct4, Sox2, Nanog and Lin28 (OSNL). They resemble embryonic stem cells (ESCs) and have the ability to differentiate into cell lineage of all three germ-layer, including cardiomyocytes (CMs). The CMs can be generated from iPSCs by inducing embryoid bodies (EBs) formation and treatment with activin A, bone morphogenic protein 4 (BMP4), and inhibitors of Wnt signaling. However, these iPSC-derived CMs are a heterogeneous population of cells and require purification and maturation to mimic the in vivo CMs. The matured CMs can be used for various therapeutic purposes in regenerative medicine by cardiomyoplasty or through the development of tissue-engineered cardiac patches. In recent years, significant advancements have been made in the isolation of iPSC and their differentiation, purification, and maturation into clinically usable CMs. Newer small molecules have also been identified to substitute the reprogramming factors for iPSC generation as well as for direct differentiation of somatic cells into CMs without an intermediary pluripotent state. This review provides a concise update on the generation of iPSC-derived CMs and their application in personalized cardiac regenerative medicine. It also discusses the current limitations and challenges in the application of iPSC-derived CMs. Graphical abstract.

Functional cardiac tissue engineering holds promise as a candidate approach for myocardial infarction. Tissue engineering has emerged to generate functional tissue constructs and provide an alternative means to repair and regenerate damaged heart tissues.

In this experimental study, we fabricated a composite polycaprolactone (PCL)/gelatine electrospun scaffold with aligned nanofibres. The electrospinning parameters and optimum proportion of the PCL/ gelatine were tested to design a scaffold with aligned and homogenized nanofibres. Using scanning electron microscopy (SEM) and mechanophysical testes, the PCL/gelatine composite scaffold with a ratio of 70:30 was selected. In order to simulate cardiac contraction, a developed mechanical loading device (MLD) was used to apply a mechanical stress with specific frequency and tensile rate to cardiac progenitor cells (CPCs) in the direction of the aligned nanofibres. Cell metabolic determination of CPCs was performed using real-time polymerase chain reaction(RT-PCR).

Physicochemical and mechanical characterization showed that the PCL/gelatine composite scaffold with a ratio of 70:30 was the best sample. In vitro analysis showed that the scaffold supported active metabolism and proliferation of CPCs, and the generation of uniform cellular constructs after five days. Real-time PCR analysis revealed elevated expressions of the specific genes for synchronizing beating cells (MYH-6, TTN and CX-43) on the dynamic scaffolds compared to the control sample with a static culture system.

Our study provides a robust platform for generation of synchronized beating cells on a nanofibre patch that can be used in cardiac tissue engineering applications in the near future.

Recent advances in biomaterials integrate metal nanoparticles with hydrogels to generate composite materials that exhibit new or improved properties. By precisely controlling the composition, arrangement and interactions of their constituents, these hybrid materials facilitate biomedical applications through myriad approaches. In this work we seek to highlight three popular frameworks for designing metal nanoparticle-hydrogel hybrid materials for biomedical applications. In the first approach, the properties of metal nanoparticles are incorporated into a hydrogel matrix such that the composite is selectively responsive to stimuli such as light and magnetic flux, enabling precisely activated therapeutics and self-healing biomaterials. The second approach mediates the dynamic reorganization of metal nanoparticles based on environment-directed changes in hydrogel structure, leading to chemosensing, microbial and viral detection, and drug-delivery capabilities. In the third approach, the hydrogel matrix spatially arranges metal nanoparticles to produce metamaterials or passively enhance nanoparticle properties to generate improved substrates for biomedical applications including tissue engineering and wound healing. This article reviews the construction, properties and biomedical applications of metal nanoparticle-hydrogel composites, with a focus on how they help to prevent, diagnose and treat diseases. Discussion includes how the composites lead to new or improved properties, how current biomedical research leverages these properties and the emerging directions in this growing field.

Cardiovascular diseases, including myocardial infarction (MI), persist as the leading cause of mortality and morbidity worldwide. The limited regenerative capacity of the myocardium presents significant challenges specifically for the treatment of MI and, subsequently, heart failure (HF). Traditional therapeutic approaches mainly rely on limiting the induced damage or the stress on the remaining viable myocardium through pharmacological regulation of remodeling mechanisms, rather than replacement or regeneration of the injured tissue. The emerging alternative regenerative medicine-based approaches have focused on restoring the damaged myocardial tissue with newly engineered functional and bioinspired tissue units. Cardiac regenerative medicine approaches can be broadly categorized into three groups: cell-based therapies, scaffold-based cardiac tissue engineering, and scaffold-free cardiac tissue engineering. Despite significant advancements, however, the clinical translation of these approaches has been critically hindered by two key obstacles for successful structural and functional replacement of the damaged myocardium, namely: poor engraftment of engineered tissue into the damaged cardiac muscle and weak electromechanical coupling of transplanted cells with the native tissue. To that end, the integration of micro- and nanoscale technologies along with recent advancements in stem cell technologies have opened new avenues for engineering of structurally mature and highly functional scaffold-based (SB-CMTs) and scaffold-free cardiac microtissues (SF-CMTs) with enhanced cellular organization and electromechanical coupling for the treatment of MI and HF. In this review article, we will present the state-of-the-art approaches and recent advancements in the engineering of SF-CMTs for myocardial repair.

Biodegradable cardiac patch is desirable to possess mechanical properties mimicking native myocardium for heart infarction treatment. We fabricated a series of anisotropic and biodegradable polyurethane porous scaffolds via thermally induced phase separation (TIPS) and tailored their mechanical properties by using various polyurethanes with different soft segments and varying polymer concentrations. The uniaxial mechanical properties, suture retention strength, ball-burst strength, and biaxial mechanical properties of the anisotropic porous scaffolds were optimized to mechanically match native myocardium. The optimal anisotropic scaffold had a ball burst strength (20.7 ± 1.5 N) comparable to that of native porcine myocardium (20.4 ± 6.0 N) and showed anisotropic behavior close to biaxial stretching behavior of the native porcine myocardium. Furthermore, the optimized porous scaffold was combined with a porcine myocardium-derived hydrogel to form a biohybrid scaffold. The biohybrid scaffold showed morphologies similar to the decellularized porcine myocardial matrix. This combination did not affect the mechanical properties of the synthetic scaffold alone. After in vivo rat subcutaneous implantation, the biohybrid scaffolds showed minimal immune response and exhibited higher cell penetration than the polyurethane scaffold alone. This biohybrid scaffold with biomimetic mechanics and good tissue compatibility would have great potential to be applied as a biodegradable acellular cardiac patch for myocardial infarction treatment.

This paper review current trends in applications of nanomaterials in tissue engineering. Nanomaterials applicable in this area can be divided into two groups: organic and inorganic. Organic nanomaterials are especially used for the preparation of highly porous scaffolds for cell cultivation and are represented by polymeric nanofibers. Inorganic nanomaterials are implemented as they stand or dispersed in matrices promoting their functional properties while preserving high level of biocompatibility. They are used in various forms (e.g., nano- particles, -tubes and -fibers)-and when forming the composites with organic matrices-are able to enhance many resulting properties (biologic, mechanical, electrical and/or antibacterial). For this reason, this contribution points especially to such type of composite nanomaterials. Basic information on classification, properties and application potential of single nanostructures, as well as complex scaffolds suitable for 3D tissues reconstruction is provided. Examples of practical usage of these structures are demonstrated on cartilage, bone, neural, cardiac and skin tissue regeneration and replacements. Nanomaterials open up new ways of treatments in almost all areas of current tissue regeneration, especially in tissue support or cell proliferation and growth. They significantly promote tissue rebuilding by direct replacement of damaged tissues.

To exploit the usability of Digital Light Processing (DLP) in regenerative medicine, biodegradable, mechanically customizable and well-defined polyester urethane acrylate resins were synthesized based on poly(caprolactone-co-trimethlenecarbonate). By controlling the monomer ratio, the resultant fabricated constructs showed tunable mechanical properties, degradation and attached hMSC morphologies.

The complex and highly organized environment in which cells reside consists primarily of the extracellular matrix (ECM) that delivers biological signals and physical stimuli to resident cells. In the native myocardium, the ECM contributes to both heart compliance and cardiomyocyte maturation and function. Thus, myocardium regeneration cannot be accomplished if cardiac ECM is not restored. We hypothesize that decellularized human skin might make an easily accessible and viable alternate biological scaffold for cardiac tissue engineering (CTE). To test our hypothesis, we decellularized specimens of both human skin and human myocardium and analyzed and compared their composition by histological methods and quantitative assays. Decellularized dermal matrix was then cut into 600-μm-thick sections and either tested by uniaxial tensile stretching to characterize its mechanical behavior or used as three-dimensional scaffold to assess its capability to support regeneration by resident cardiac progenitor cells (hCPCs) in vitro. Histological and quantitative analyses of the dermal matrix provided evidence of both effective decellularization with preserved tissue architecture and retention of ECM proteins and growth factors typical of cardiac matrix. Further, the elastic modulus of the dermal matrix resulted comparable with that reported in literature for the human myocardium and, when tested in vitro, dermal matrix resulted a comfortable and protective substrate promoting and supporting hCPC engraftment, survival and cardiomyogenic potential. Our study provides compelling evidence that dermal matrix holds promise as a fully autologous and cost-effective biological scaffold for CTE.

The number of people affected by heart disease such as coronary artery disease and myocardial infarction increases at an alarming rate each year. Currently, the methods to treat these diseases are restricted to lifestyle change, pharmaceuticals, and eventually heart transplant if the condition is severe enough. While these treatment options are the standard for caring for patients who suffer from heart disease, limited regenerative ability of the heart restricts the effectiveness of treatment and may lead to other heart-related health problems in the future. Because of the increasing need for more effective therapeutic technologies for treating diseased heart tissue, cardiac patches are now a large focus for researchers. The cardiac patches are designed to be integrated into the patients' natural tissue to introduce mechanical support and healing to the damaged areas. As a promising alternative, synthetic biodegradable polymer based biomaterials can be easily manipulated to customize material properties, as well as possess certain desired characteristics for cardiac patch use. This comprehensive review summarizes recent works on synthetic biodegradable cardiac patches implanted into infarcted animal models. In addition, this review describes the basic requirements that should be met for cardiac patch development, and discusses the inspirations to designing new biomaterials and technologies for cardiac patches.

Patients suffering from heart failure often require circulatory support using ventricular assist devices (VADs). However, most existing VADs provide nonpulsatile flow, involve direct contact between the blood flow and the device's lumen and moving components, and require a driveline to connect to an external power source. These design features often lead to complications such as gastrointestinal bleeding, device thrombosis, and driveline infections. Here, a concept of magnetically active cardiac patches (MACPs) that can potentially function as non-blood contacting, untethered pulsatile VADs inside a magnetic actuationsystem is reported. The MACPs, which are composed of permanent magnets and 3D-printed patches, are attached to the epicardial surfaces, thus avoiding direct contact with the blood flow. They provide powerful actuation assisting native heart pumping inside a magnetic actuation system. In ex vivo experiments on a healthy pig's heart, it is shown that the ventricular ejection fractions are as high as 37% in the left ventricle and 63% in the right ventricle. Non-blood contacting, untethered VADs can eliminate the risk of serious complications associated with existing devices, and provide an alternative solution for myocardial training and therapy for patients with heart failure.

3D scaffolds used to repair damaged tissues should be able to mimic both composition and functions of natural extracellular matrix, which is mainly composed of polysaccharides and proteins. In our previous research new biomimetic sponges, based on blends of alginate with gelatin, were produced and characterized for myocardial tissue engineering applications. It was observed that these scaffolds can potentially function as a promising cardiac extracellular matrix substitute, but a reinforcement is required to improve their suturing properties. Aim of the present work was the development of a suturable biomimetic patch by the inclusion of a synthetic mesh within an alginate/gelatin scaffold. The mesh, produced by dry spinning, was made of eight superimposed layers of polycaprolactone microfibers, each one rotated of 45° with respect to the adjacent one. Reinforced scaffolds were obtained through the use of a mold, specially designed to place the fibrous mesh exactly in the center of the sponge. Both the reinforcement mesh and the reinforced scaffold were characterized. A perfect integration between the mesh and the sponge was observed. The fibrous mesh reduced the capacity of the sponge to absorb water, but the degree of hydrophilicity of the material was still comparable with that of natural cardiac tissue. The reinforced system showed a suitable stability in aqueous environment and it resulted much more resistant to suturing than not reinforced scaffold and even than human arteries. Polycaprolactone mesh was not cytotoxic and the reinforced scaffold was able to support cardiomyocytes adhesion and proliferation. Overall, the obtained results confirmed that the choice to modify the alginate/gelatin sponges through the insertion of an appropriate reinforcement system turned out to be correct in view of their potential use in myocardial tissue engineering.

Once focused exclusively on the creation of tissues to repair or replace diseased or damaged organs, the field of tissue engineering has undergone an important evolution in recent years. Namely, tissue engineering techniques are increasingly being applied to intentionally generate pathological conditions. Motivated in part by the wide gap between 2D cultures and animal models in the current disease modeling continuum, disease-inspired tissue-engineered platforms have numerous potential applications, and may serve to advance our understanding and clinical treatment of various diseases. This review will focus on recent progress toward generating tissue-engineered models of cardiovascular diseases, including cardiac hypertrophy, fibrosis, and ischemia reperfusion injury, atherosclerosis, and calcific aortic valve disease, with an emphasis on how these disease-inspired platforms can be used to decipher disease etiology. Each pathology is discussed in the context of generating both disease-specific cells as well as disease-specific extracellular environments, with an eye toward future opportunities to integrate different tools to yield more complex and physiologically relevant culture platforms. Ultimately, the development of effective disease treatments relies upon our ability to develop appropriate experimental models; as cardiovascular diseases are the leading cause of death worldwide, the insights yielded by improved in vitro disease modeling could have substantial ramifications for public health and clinical care.

Cardiovascular tissue engineering endeavors to repair or regenerate damaged or ineffective blood vessels, heart valves, and cardiac muscle. Current strategies that aim to accomplish such a feat include the differentiation of multipotent or pluripotent stem cells on appropriately designed biomaterial scaffolds that promote the development of mature and functional cardiac tissue. The advent of additive manufacturing 3D bioprinting technology further advances the field by allowing heterogenous cell types, biomaterials, and signaling factors to be deposited in precisely organized geometries similar to those found in their native counterparts. Bioprinting techniques to fabricate cardiac tissue in vitro include extrusion, inkjet, laser-assisted, and stereolithography with bioinks that are either synthetic or naturally-derived. The article further discusses the current practices for postfabrication conditioning of 3D engineered constructs for effective tissue development and stability, then concludes with prospective points of interest for engineering cardiac tissues in vitro. Cardiovascular three-dimensional bioprinting has the potential to be translated into the clinical setting and can further serve to model and understand biological principles that are at the root of cardiovascular disease in the laboratory.

Given their durability and long-term stability, self-healable hydrogels have, in the past few years, emerged as promising replacements for the many brittle hydrogels currently being used in preclinical or clinical trials. To this end, the incompatibility between hydrogel toughness and rapid self-healing remains unaddressed, and therefore most of the self-healable hydrogels still face serious challenges within the dynamic and mechanically demanding environment of human organs/tissues. Furthermore, depending on the target tissue, the self-healing hydrogels must comply with a wide range of properties including electrical, biological, and mechanical. Notably, the incorporation of nanomaterials into double-network hydrogels is showing great promise as a feasible way to generate self-healable hydrogels with the above-mentioned attributes. Here, the recent progress in the development of multifunctional and self-healable hydrogels for various tissue engineering applications is discussed in detail. Their potential applications within the rapidly expanding areas of bioelectronic hydrogels, cyborganics, and soft robotics are further highlighted.

Decellularized extracellular matrix (dECM) derived from myocardium has been widely explored as a nature scaffold for cardiac tissue engineering applications. Cardiac dECM offers many unique advantages such as preservation of organ-specific ECM microstructure and composition, demonstration of tissue-mimetic mechanical properties and retention of biochemical cues in favor of subsequent recellularization. However, current processes of dECM decellularization and recellularization still face many challenges including the need for balance between cell removal and extracellular matrix preservation, efficient recellularization of dECM for obtaining homogenous cell distribution, tailoring material properties of dECM for enhancing bioactivity and prevascularization of thick dECM. This review summarizes the recent progresses of using dECM scaffold for cardiac repair and discusses its major advantages and challenges for producing biomimetic cardiac patch.

Three-dimensional (3D) bioprinting is a promising technique used to fabricate scaffolds from hydrogels with living cells. However, the printability of hydrogels in bioprinting has not been adequately studied. The aim of this study was to quantitatively characterize the printability and cell viability of alginate dialdehyde (ADA)-gelatin (Gel) hydrogels for bioprinting. ADA-Gel hydrogels of various concentrations were synthesized and characterized using Fourier transform infrared spectroscopy, along with rheological tests for measuring storage and loss moduli. Scaffolds (with an area of 11 × 11 mm) of 1, 2, and 13 layers were fabricated from ADA-Gel hydrogels using a 3D-bioplotter under printing conditions with and without the use of cross-linker, respectively, at room temperature and at 4 °C. Scaffolds were then quantitatively assessed in terms of the minimum printing pressure, quality of strands and pores, and structural integrity, which were combined together for the characterization of ADA-Gel printability. For the assessment of cell viability, scaffolds were bioprinted from ADA-Gel hydrogels with human umbilical vein endothelial cells (HUVECs) and rat Schwann cells and were then examined at day 7 with live/dead assay. HUVECs and Schwann cells were used as models to demonstrate biocompatibility for potential angiogenesis and nerve repair applications, respectively. Our results illustrated that ADA-Gel hydrogels with a loss tangent (ratio of loss modulus over storage modulus) between 0.24 and 0.28 could be printed in cross-linker with the best printability featured by uniform strands, square pores, and good structural integrity. Additionally, our results revealed that ADA-Gel hydrogels with an appropriate printability could maintain cell viability over 7 days. Combined together, this study presents a novel method to characterize the printability of hydrogels in bioprinting and illustrates that ADA-Gel hydrogels can be synthesized and bioprinted with good printability and cell viability, thus demonstrating their suitability for bioprinting scaffolds in tissue engineering applications.