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Myocardial infarction (MI), which causes irreversible myocardium necrosis, affects 0.25 billion people globally and has become one of the most significant epidemics of our time. Over the past few years, bioprinting has moved beyond a concept of simply incorporating cells into biomaterials, to strategically defining the microenvironment (e.g., architecture, biomolecular signalling, mechanical stimuli, etc.) within which the cells are printed. Among the different bioprinting applications, myocardial repair is a field that has seen some of the most significant advances towards the management of the repaired tissue microenvironment. This review critically assesses the most recent biomedical innovations being carried out in cardiac patch bioprinting, with specific considerations given to the biomaterial design parameters, growth factors/cytokines, biomechanical and bioelectrical conditioning, as well as innovative biomaterial-based "4D" bioprinting (3D scaffold structure + temporal morphology changes) of myocardial tissues, immunomodulation and sustained delivery systems used in myocardium bioprinting. Key challenges include the ability to generate large quantities of cardiac cells, achieve high-density capillary networks, establish biomaterial designs that are comparable to native cardiac extracellular matrix, and manage the sophisticated systems needed for combining cardiac tissue microenvironmental cues while simultaneously establishing bioprinting technologies yielding both high-speed and precision. This must be achieved while considering quality assurance towards enabling reproducibility and clinical translation. Moreover, this manuscript thoroughly discussed the current clinical translational hurdles and regulatory issues associated with the post-bioprinting evaluation, storage, delivery and implantation of the bioprinted myocardial patches. Overall, this paper provides insights into how the clinical feasibility and important regulatory concerns may influence the design of the bioink (biomaterials, cell sources), fabrication and post-fabrication processes associated with bioprinting of the cardiac patches. This paper emphasizes that cardiac patch bioprinting requires extensive collaborations from imaging and 3D modelling technical experts, biomaterial scientists, additive manufacturing experts and healthcare professionals. Further, the work can also guide the field of cardiac patch bioprinting moving forward, by shedding light on the potential use of robotics and automation to increase productivity, reduce financial cost, and enable standardization and true commercialization of bioprinted cardiac patches. The manuscript provides a critical review of important themes currently pursued for heart patch bioprinting, including critical biomaterial design parameters, physiologically-relevant cardiac tissue stimulations, and newly emerging cardiac tissue bioprinting strategies. This review describes the limited number of studies, to date in the literature, that describe systemic approaches to combine multiple design parameters, including capabilities to yield high-density capillary networks, establish biomaterial composite designs similar to native cardiac extracellular matrix, and incorporate cardiac tissue microenvironmental cues, while simultaneously establishing bioprinting technologies that yield high-speed and precision. New tools such as artificial intelligence may provide the analytical power to consider multiple design parameters and identify an optimized work-flow(s) for enabling the clinical translation of bioprinted cardiac patches. [Display omitted] [ABSTRACT FROM AUTHOR]

Recent progress in developing cardiac patches for regenerating the myocardium has opened a new hope after myocardial infarction (MI). Herein, we introduce a novel bilayer nanofiber cardiac patch composed of polycaprolactone (PCL), poly(xylitol sebacate) (PXS), and multi-walled carbon nanotubes (MWCNTs). First, we electrospun different monolayer scaffolds, including PCL, PCL/MWCNT, PCL/PXS, and PCL/PXS/MWCNTs, and characterized their physical, mechanical, and biological performance to determine the interaction effects of different material compositions on their scaffold properties. In vitro examinations confirmed the cooperative effect of PXS and MWCNT in blending with PCL to fabricate conductive and well-organized nanofibers with good biocompatibility. Subsequently, a bilayer nanofiber scaffold composed of PCL/PXS/MWCNT nanofibers electrospun over a PCL fibrous layer was fabricated to achieve an efficient structure capable of providing the desirable characteristics of a cardiac patch. The bilayer nature increased the mechanical performance of the PCL/PXS/MWCNT monolayer while preserving its appropriate wettability and acceptable conductivity. Excellent viability and proliferation of H9c2 cells on the bilayer scaffolds were observed in the live/dead assay. Moreover, cell-matrix interaction confirmed that bilayer nanofibers decrease myofibroblast differentiation of seeded NIH3T3 cells, which may be beneficial for cardiac repair post-MI. After transplantation of the bilayer nanofiber onto the infarcted heart of the MI rats for 4 weeks, the ischemic zone decreased, cardiac function significantly improved and very slightly activated macrophages were observed. These findings suggested a potentially durable nanofiber cardiac patch containing PXS for myocardial repair post-MI. [ABSTRACT FROM AUTHOR]

In recent years, injectable hydrogels and cardiac patches have provided a promising approach to improve cardiac regeneration and function after myocardial infarction, however, the crucial designing factors of these biomaterials have been less reviewed. Therefore, in this review, we speculate on the prominent design parameters. A profound understanding of the main properties of native heart tissue can guide the efforts to obtain biomaterials with desirable biomimicking properties that improve the effectiveness of future fabricated myocardial biomaterials. Moreover, the injectable hydrogels and cardiac patches with reactive oxygen species scavenging properties will be reviewed in detail owing to the promising results of in vitro and in vivo studies on cardiac regeneration after myocardial infarction. This review can pave the way for an optimized design for effective cardiac biomaterials by considering the optimum ranges for physical, chemical, and biological characteristics of biomaterials, as well as the study of undetected parameters that can be investigated in future studies. [ABSTRACT FROM AUTHOR]

Myocardial infarction is one of the main causes of death worldwide. After myocardial infarction, the damaged area is typically occupied with non‐contractile scar tissue owing to the limited ability of cardiac cells to proliferate. Cardiac patches can potentially restore heart function by providing sufficient electrochemical properties to the damaged area and supporting the differentiation into and proliferation of cardiac cells. In this study, we developed for the first time a poly(mannitol sebacate) (PMS) based scaffold combined with 1% (w/w)multi‐walled carbon nanotubes (MWCNTs) to produce a biocompatible cardiac patch by the solvent casting method. We characterized the resultant PMS‐MWCNT scaffold in terms of chemical, physical, mechanical and electrical properties. The PMS/MWCNT patch revealed appropriate hydrophilicity, elasticity close to that of the target tissue, and electrical conductivity suited for a cardiac patch. The cytocompatibility of the composite was confirmed by the successful attachment and proliferation of human umbilical cord mesenchymal stem cells (HUC‐MSCs). The PMS/MWCNTs further contributed to the differentiation of HUC‐MSCs by significant overexpression of cardiac‐specific proteins, i.e. troponin T and connexin 43, in the presence of 5‐azacytidine. The findings of this study could be of assistance in the use and development of PMS‐based composites as cardiac patches for myocardial tissue engineering applications. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Engineering cardiac implants for treating myocardial infarction (MI) has advanced, but challenges persist in mimicking the structural properties and variability of cardiac tissues using traditional bioconstructs and conventional engineering methods. This study introduces a synthetic patch with a bioactive surface designed to swiftly restore functionality to the damaged myocardium. The patch combines a composite, soft, and conductive hydrogel‐based on (3,4‐ethylenedioxythiophene):polystyrene‐sulfonate (PEDOT:PSS) and polyvinyl alcohol (PVA). This cardiac patch exhibits a reasonably high electrical conductivity (40 S/cm) and a stretchability up to 50% of its original length. Our findings reveal its resilience to 10% cyclic stretching at 1 Hz with no loss of conductivity over time. To mediate a strong cell–scaffold adhesion, we biofunctionalize the hydrogel with a N‐cadherin mimic peptide, providing the cardiac patch with a bioactive surface. This modification promote increased adherence and proliferation of cardiac fibroblasts (CFbs) while effectively mitigating the formation of bacterial biofilm, particularly against Staphylococcus aureus, a common pathogen responsible for surgical site infections (SSIs). Our study demonstrates the successful development of a structurally validated cardiac patch possessing the desired mechanical, electrical, and biofunctional attributes for effective cardiac recovery. Consequently, this research holds significant promise in alleviating the burden imposed by myocardial infarctions. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (MI) leads to a loss of cardiac function which, following adverse ventricular remodeling (AVR), can ultimately result in heart failure. Tissue-engineered contractile patches placed over the infarct offer potential for restoring cardiac function and reducing AVR. In this computational study, we investigate how improvement of pump function depends on the orientation of the cardiac patch and the fibers therein relative to the left ventricle (LV). Additionally, we examine how model outcome depends on the choice of material properties for healthy and infarct tissue. In a finite element model of LV mechanics, an infarction was induced by eliminating active stress generation and increasing passive tissue stiffness in a region comprising 15% of the LV wall volume. The cardiac patch was modeled as a rectangular piece of healthy myocardium with a volume of 25% of the infarcted tissue. The orientation of the patch was varied from 0 to 150 ∘ relative to the circumferential plane. The infarct reduced stroke work by 34% compared to the healthy heart. Optimal patch support was achieved when the patch was oriented parallel to the subepicardial fiber direction, restoring 9% of lost functionality. Typically, about one-third of the total recovery was attributed to the patch, while the remainder resulted from restored functionality in native myocardium adjacent to the infarct. The patch contributes to cardiac function through two mechanisms. A contribution of tissue in the patch and an increased contribution of native tissue, due to favorable changes in mechanical boundary conditions. [ABSTRACT FROM AUTHOR]

Applied to the epicardium in-vivo , regenerative cardiac patches support the ventricular wall, reduce wall stresses, encourage ventricular wall thickening, and improve ventricular function. Scaffold engraftment, however, remains a challenge. After implantation, scaffolds are subject to the complex, time-varying, biomechanical environment of the myocardium. The mechanical capacity of engineered tissue to biomimetically deform and simultaneously support the damaged native tissue is crucial for its efficacy. To date, however, the biomechanical response of engineered tissue applied directly to live myocardium has not been characterized. In this paper, we utilize optical imaging of a Langendorff ex-vivo cardiac model to characterize the native deformation of the epicardium as well as that of attached engineered scaffolds. We utilize digital image correlation, linear strain, and 2D principal strain analysis to assess the mechanical compliance of acellular ice templated collagen scaffolds. Scaffolds had either aligned or isotropic porous architecture and were adhered directly to the live epicardial surface with either sutures or cyanoacrylate glue. We demonstrate that the biomechanical characteristics of native myocardial deformation on the epicardial surface can be reproduced by an ex-vivo cardiac model. Furthermore, we identified that scaffolds with unidirectionally aligned pores adhered with suture fixation most accurately recapitulated the deformation of the native epicardium. Our study contributes a translational characterization methodology to assess the physio-mechanical performance of engineered cardiac tissue and adds to the growing body of evidence showing that anisotropic scaffold architecture improves the functional biomimetic capacity of engineered cardiac tissue. Engineered cardiac tissue offers potential for myocardial repair, but engraftment remains a challenge. In-vivo , engineered scaffolds are subject to complex biomechanical stresses and the mechanical capacity of scaffolds to biomimetically deform is critical. To date, the biomechanical response of engineered scaffolds applied to live myocardium has not been characterized. In this paper, we utilize optical imaging of an ex-vivo cardiac model to characterize the deformation of the native epicardium and scaffolds attached directly to the heart. Comparing scaffold architecture and fixation method, we demonstrate that sutured scaffolds with anisotropic pores aligned with the native alignment of the superficial myocardium best recapitulate native deformation. Our study contributes a physio-mechanical characterization methodology for cardiac tissue engineering scaffolds. [Display omitted] [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is one of the major diseases that threaten human life and health. The construction of cardiac patch by tissue engineering method and biomaterials is a promising way to treat MI clinically by improving electromechanical signal transduction in MI area. A highly conductive electrospun fibre-engineered biomedical patch with porous structure, mechanical support and conductive property was prepared by poly(lactic-co-glycolic acid) (PLGA), polyaniline (PANI), graphene oxide (GO) and multi-walled carbon nanotubes (MWCNT). PLGA, PLGA/MWCNT, PLGA/GO electrospinning fibre membrane substrates were prepared first and then in-situ polymerization of aniline (ANI) to form PANI/PLGA and PANI/PLGA/MWCNT fibre conductive patches. PLGA-blended fibre patch had a smooth fibre surface and an uniform fibre diameter, porous structure, fibre parallel arrangement, in which PLGA/MWCNT had larger ultimate strength and Young’s modulus. When the ANI concentration was 0.4 mol l−1, electrical conductivity reached the maximum value, and the electrical conductivity of PANI/PLGA fibre patch was significantly larger than that of PANI/PLGA/MWCNT fibre patch as the ANI concentration increased, which were 1.56 × 10−2 and 6.06 × 10−3 S cm−1, respectively. Highly conductive fibre membrane-engineered biomedical patch had excellent electrical and thermal stability, and improved signal transduction, with porous structure and mechanical support for potential MI repair. [ABSTRACT FROM AUTHOR]

Since cardiovascular diseases (CVDs) are globally one of the leading causes of death, of which myocardial infarction (MI) can cause irreversible damage and decrease survivors' quality of life, novel therapeutics are needed. Current approaches such as organ transplantation do not fully restore cardiac function or are limited. As a valuable strategy, tissue engineering seeks to obtain constructs that resemble myocardial tissue, vessels, and heart valves using cells, biomaterials as scaffolds, biochemical and physical stimuli. The latter can be induced using a bioreactor mimicking the heart's physiological environment. An extensive review of bioreactors providing perfusion, mechanical and electrical stimulation, as well as the combination of them is provided. An analysis of the stimulations' mechanisms and modes that best suit cardiac construct culture is developed. Finally, we provide insights into bioreactor configuration and culture assessment properties that need to be elucidated for its clinical translation. [ABSTRACT FROM AUTHOR]

Melt electrowriting (MEW) is an electric-field-assisted additive biofabrication technique that has brought significant advancements to bioinspired scaffold design for soft tissue engineering and beyond. Owing to its targeted microfiber placement, MEW has become a powerful platform technology for the fabrication of in vitro disease models up to functional biohybrid constructs that are investigated in vivo to reach clinical translation soon. This work provides a concise overview of this rapidly evolving field by highlighting the key contributions of MEW to cardiovascular tissue engineering. Specifically, we i) pinpoint the methods to introduce microvascular networks in thick 3D constructs benefitting from (sacrificial) MEW microfibers, ii) report MEW-based concepts for small-diameter vascular grafts and stents, iii) showcase how contracting cardiac tissues can profit from the tunable structure–property relationship of MEW scaffolds, and iv) address how complete regenerative heart valves can be built on complex fiber scaffold architectures that recapitulate J-shaped tensile properties and tissue heterogeneity. Lastly, we touch on novel biomaterial advancements and discuss the technological challenges of MEW to unlock the full potential of this transformative technology.

Cell implantation offers an appealing avenue for heart repair after myocardial infarction (MI). Nevertheless, the implanted cells are subjected to the aberrant myocardial niche, which inhibits cell survival and maturation, posing significant challenges to the ultimate therapeutic outcome. The functional cardiac patches (CPs) have been proved to construct an elastic conductive, antioxidative, and angiogenic microenvironment for rectifying the aberrant microenvironment of the infarcted myocardium. More importantly, inducing implanted cardiomyocytes (CMs) adapted to the anisotropic arrangement of myocardial tissue by bioengineered structural cues within CPs are more conducive to MI repair. Herein, a functional Cig/(TA-Cu) CP served as biomimetic cardiac niche was fabricated based on structural anisotropic cigarette filter by modifying with tannic acid (TA)-chelated Cu2+ (TA-Cu complex) via a green method. This CP possessed microstructural anisotropy, electrical conductivity and mechanical properties similar to natural myocardium, which could promote elongation, orientation, maturation, and functionalization of CMs. Besides, the Cig/(TA-Cu) CP could efficiently scavenge reactive oxygen species, reduce CM apoptosis, ultimately facilitating myocardial electrical integration, promoting vascular regeneration and improving cardiac function. Together, our study introduces a functional CP that integrates multimodal cues to create a biomimetic cardiac niche and provides an effective strategy for cardiac repair.

Myocardial infarction is one of the leading causes of death globally and in most cases, heart transplantation is required. As an alternative to heart transplantation, engineered cardiac patches have been recently developed as a potential solution for restoring cardiac function. Engineering a cardiac patch necessitates tailoring various design criteria mainly including materials, i.e., natural and/or synthetic, mechanical and physical properties, and fabrication method. Here, we review and examine the latest research on design of engineered cardiac patches and provide a critical analysis and direction for future works. [ABSTRACT FROM AUTHOR]

The infarcted heart undergoes irreversible pathological remodeling after reperfusion involving left ventricle dilation and excessive inflammatory reactions in the infarcted heart, frequently leading to fatal functional damage. Extensive attempts have been made to attenuate pathological remodeling in infarcted hearts using cardiac patches and anti-inflammatory drug delivery. In this study, we developed a paintable and adhesive hydrogel patch using dextran-aldehyde (dex-ald) and gelatin, incorporating the anti-inflammatory protein, ANGPTL4, into the hydrogel for sustained release directly to the infarcted heart to alleviate inflammation. We optimized the material composition, including polymer concentration and molecular weight, to achieve a paintable, adhesive hydrogel using 10% gelatin and 5% dex-ald, which displayed in-situ gel formation within 135 s, cardiac tissue-like modulus (40.5 kPa), suitable tissue adhesiveness (4.3 kPa), and excellent mechanical stability. ANGPTL4 was continuously released from the gelatin/dex-ald hydrogel without substantial burst release. The gelatin/dex-ald hydrogel could be conveniently painted onto the beating heart and degraded in vivo. Moreover, in vivo studies using animal models of acute myocardial infarction revealed that our hydrogel cardiac patch containing ANGPTL4 significantly improved heart tissue repair, evaluated by echocardiography and histological evaluation. The heart tissues treated with ANGPTL4-loaded hydrogel patches exhibited increased vascularization, reduced inflammatory macrophages, and structural maturation of cardiac cells. Our novel hydrogel system, which allows for facile paintability, appropriate tissue adhesiveness, and sustained release of anti-inflammatory drugs, will serve as an effective platform for the repair of various tissues, including heart, muscle, and cartilage.

Adverse ventricular remodeling following acute myocardial infarction (MI) may induce ventricular dilation, fibrosis, and loss of global contractile function, possibly resulting in heart failure (HF). Understanding the relation between the time-dependent changes in material properties of the myocardium and the contractile function of the heart may further our understanding of the development of HF post-MI and guide the development of novel therapies. A finite element model of cardiac mechanics was used to model MI in a thick-walled truncated ellipsoidal geometry. Infarct core and border zone comprised 9.6 and 8.1% of the LV wall volume, respectively. Acute MI was modeled by inhibiting active stress generation. Chronic MI was modeled by the additional effect of infarct material stiffening, wall thinning and fiber reorientation. In acute MI, stroke work decreased by 25%. In the infarct core, fiber stress was reduced but fiber strain was increased, depending on the degree of infarct stiffening. Fiber work density was equal to zero. Healthy tissue adjacent to the infarct showed decreased work density depending on the degree of infarct stiffness and the orientation of the myofibers with respect to the infarct region. Thinning of the wall partially restored this loss in work density while the effects of fiber reorientation were minimal. We found that the relative loss in pump function in the infarcted heart exceeds the relative loss in healthy myocardial tissue due to impaired mechanical function in healthy tissue adjacent to the infarct. Infarct stiffening, wall thinning and fiber reorientation did not affect pump function but did affect the distribution of work density in tissue adjacent to the infarct. [ABSTRACT FROM AUTHOR]

Abstract Myocardial infarction (MI) is a cardiovascular emergency and the leading cause of death worldwide. Inflammatory and immune responses are initiated immediately after MI, leading to myocardial death, scarring, and ventricular remodeling. Current therapeutic approaches emphasize early restoration of ischemic myocardial reperfusion, but there is no effective treatment for the pathological changes of infarction. Biomedical materials development has brought new hope for MI diagnosis and treatment. Biomedical materials, such as cardiac patches, hydrogels, nano biomaterials, and artificial blood vessels, have played an irreplaceable role in MI diagnosis and treatment. They improve the accuracy and efficacy of MI diagnosis and offer further possibilities for reducing inflammation, immunomodulation, inhibiting fibrosis, and cardiac regeneration. This review focuses on the advances in biomedical materials applications in MI diagnosis and treatment. The current studies are outlined in terms of mechanisms of action and effects. It is addressed how biomedical materials application can lessen myocardial damage, encourage angiogenesis, and enhance heart function. Their clinical transformation value and application prospect are discussed.

Application of cardiac patches to the heart surface can be undertaken to provide support and facilitate regeneration of the damaged cardiac tissue following ischemic injury. Biomaterial composition is an important consideration in the design of cardiac patch materials as it governs host response to ultimately prevent the undesirable fibrotic response. Here, we investigate a novel patch material, poly (itaconate-co-citrate-co-octanediol) (PICO), in the context of cardiac implantation. Citric acid (CA) and itaconic acid (ITA), the molecular components of PICO, provided a level of protection for cardiac cells during ischemic reperfusion injury in vitro. Biofabricated PICO patches were shown to degrade in accelerated and hydrolytic conditions, with CA and ITA being released upon degradation. Furthermore, the host response to PICO patches after implantation on rat epicardium in vivo was explored and compared to two biocompatible cardiac patch materials, poly (octamethylene (anhydride) citrate) (POMaC) and poly (ethylene glycol) diacrylate (PEGDA). PICO patches resulted in less macrophage infiltration and lower foreign body giant cell reaction compared to the other materials, with corresponding reduction in smooth muscle actin-positive vessel infiltration into the implant region. Overall, this work demonstrates that PICO patches release CA and ITA upon degradation, both of which demonstrate cardioprotective effects on cardiac cells after ischemic injury, and that PICO patches generate a reduced inflammatory response upon implantation to the heart compared to other materials, signifying promise for use in cardiac patch applications.

Myocardial infarction (MI) is one of the leading causes of death and disability. Recently developed cardiac patches provide mechanical support and additional conductive paths to promote electrical signal propagation in the MI area to synchronize cardiac excitation and contraction. Cardiac patches based on conductive polymers offer attractive features; however, the modest levels of elasticity and high impedance interfaces limit their mechanical and electrical performance. These structures also operate as permanent implants, even in cases where their utility is limited to the healing period of tissue damaged by the MI. The work presented here introduces a highly conductive cardiac patch that combines bioresorbable metals and polymers together in a hybrid material structure configured in a thin serpentine geometry that yields elastic mechanical properties. Finite element analysis guides optimized choices of layouts in these systems. Regular and synchronous contraction of human induced pluripotent stem cell‐derived cardiomyocytes on the cardiac patch and ex vivo studies offer insights into the essential properties and the bio‐interface. These results provide additional options in the design of cardiac patches to treat MI and other cardiac disorders. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of death in the United States, which can result in blockage of a coronary artery, triggering a myocardial infarction (MI), scar tissue formation in the myocardium, and ultimately heart failure. Currently, the gold‐standard solution for total heart failure is a heart transplantation. An alternative to total‐organ transplantation is surgically remodeling the ventricle with the implantation of a cardiac patch. Acellular cardiac patches have previously been investigated using synthetic or decellularized native materials to improve cardiac function. However, a limitation of this strategy is that acellular cardiac patches only reshape the ventricle and do not increase cardiac contractile function. Toward the development of a cardiac patch, our laboratory previously developed a cell‐populated composite fibrin scaffold and aligned microthreads to recapitulate the mechanical properties of native myocardium. In this study, we explore micropatterning the surfaces of fibrin gels to mimic anisotropic native tissue architecture and promote cellular alignment of human induced pluripotent stem cell cardiomyocytes (hiPS‐CM), which is crucial for increasing scaffold contractile properties. hiPS‐CMs seeded on micropatterned surfaces exhibit cellular elongation, distinct sarcomere alignment, and circumferential connexin‐43 staining at 14 days of culture, which are necessary for mature contractile properties. Constructs were also subject to electrical stimulation during culture to promote increased contractile properties. After 7 days of stimulation, contractile strains of micropatterned constructs were significantly higher than unpatterned controls. These results suggest that the use of micropatterned topographic cues on fibrin scaffolds may be a promising strategy for creating engineered cardiac tissue. [ABSTRACT FROM AUTHOR]

Abstract Myocardial infarction (MI) is one of the leading causes of death and disability. Recently developed cardiac patches provide mechanical support and additional conductive paths to promote electrical signal propagation in the MI area to synchronize cardiac excitation and contraction. Cardiac patches based on conductive polymers offer attractive features; however, the modest levels of elasticity and high impedance interfaces limit their mechanical and electrical performance. These structures also operate as permanent implants, even in cases where their utility is limited to the healing period of tissue damaged by the MI. The work presented here introduces a highly conductive cardiac patch that combines bioresorbable metals and polymers together in a hybrid material structure configured in a thin serpentine geometry that yields elastic mechanical properties. Finite element analysis guides optimized choices of layouts in these systems. Regular and synchronous contraction of human induced pluripotent stem cell‐derived cardiomyocytes on the cardiac patch and ex vivo studies offer insights into the essential properties and the bio‐interface. These results provide additional options in the design of cardiac patches to treat MI and other cardiac disorders.

Myocardial infarction (MI) is a cardiovascular emergency and the leading cause of death worldwide. Inflammatory and immune responses are initiated immediately after MI, leading to myocardial death, scarring, and ventricular remodeling. Current therapeutic approaches emphasize early restoration of ischemic myocardial reperfusion, but there is no effective treatment for the pathological changes of infarction. Biomedical materials development has brought new hope for MI diagnosis and treatment. Biomedical materials, such as cardiac patches, hydrogels, nano biomaterials, and artificial blood vessels, have played an irreplaceable role in MI diagnosis and treatment. They improve the accuracy and efficacy of MI diagnosis and offer further possibilities for reducing inflammation, immunomodulation, inhibiting fibrosis, and cardiac regeneration. This review focuses on the advances in biomedical materials applications in MI diagnosis and treatment. The current studies are outlined in terms of mechanisms of action and effects. It is addressed how biomedical materials application can lessen myocardial damage, encourage angiogenesis, and enhance heart function. Their clinical transformation value and application prospect are discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Although the use of cardiac patches is still controversial, cardiac patch has the significance in the field of the tissue engineered cardiac regeneration because it overcomes several shortcomings of intra-myocardial injection by providing a template for cells to form a cohesive sheet. So far, fibrous scaffolds fabricated using electrospinning technique have been increasingly explored for preparation of cardiac patches. One of the problems with the use of electrospinning is that nanofibrous structures hardly allow the infiltration of cells for development of 3D tissue construct. In this respect, we have prepared novel bi-modal electrospun scaffolds as a feasible strategy to address the challenges in cardiac tissue engineering . Methods Nano/micro bimodal composite fibrous patch composed of collagen and poly (D, L-lactic-co-glycolic acid) (Col/PLGA) was fabricated using an independent nozzle control multi-electrospinning apparatus, and its feasibility as the stem cell laden cardiac patch was systemically investigated. Results Nano/micro bimodal distributions of Col/PLGA patches without beaded fibers were obtained in the range of the 4-6% collagen concentration. The poor mechanical properties of collagen and the hydrophobic property of PLGA were improved by co-electrospinning. In vitro experiments using bone marrow-derived mesenchymal stem cells (BMSCs) revealed that Col/PLGA showed improved cyto-compatibility and proliferation capacity compared to PLGA, and their extent increased with increase in collagen content. The results of tracing nanoparticle-labeled as well as GFP transfected BMSCs strongly support that Col/PLGA possesses the long-term stem cells retention capability, thereby allowing stem cells to directly function as myocardial and vascular endothelial cells or to secrete the recovery factors, which in turn leads to improved heart function proved by histological and echocardiographic findings. Conclusion Col/PLGA bimodal cardiac patch could significantly attenuate cardiac remodeling and fully recover the cardiac function, as a consequence of their potent long term stem cell engraftment capability.

To promote the differentiation of human-induced pluripotent stem cells (hiPSCs) into myocardium through a standard chemically defined and small-molecule-based induction protocol (CDM3), and preliminarily prepare myocardial patches that provide experimental data and theoretical support for further maturation through other in vitro experiments and safety studies in vivo. After resuscitation, culture, and identification of hiPSCs, they were inoculated onto Matrigel-coated polycaprolactone (PCL). After 24 h, cell growth was observed by DAPI under a fluorescence microscope and the stemness of hiPSCs was identified by OCT4 fluorescence. After fixation, scanning electron microscopy was performed to observe the morphology of cells on the patch surface. On days 1, 3, 5, and 7 of culture, cell viability was determined by Cell Counting Kit-8 (CCK-8) assay and a curve was drawn to observe cell growth and proliferation. After co-culture with Matrigel-covered PCL for 24 h, hiPSCs were divided into control and CDM3 groups, and cultured for an additional 6 d. On the eighth day, cell growth was observed by DAPI under a fluorescence microscope, hiPSC stemness was identified by OCT4 fluorescence, and cardiomyocytes were identified by cardiac troponin T (cTnT) and α-actin expression. hiPSCs co-cultured with Matrigel-covered PCL for 24 h emitted green fluorescence indicating OCT4, showing that hiPSCs maintained their stemness on Matrigel-covered PCL scaffolds. DAPI emitted blue fluorescence, indicating that cells grew clonally with uniform cell morphology. Scanning electron microscopy showed that hiPSCs adhered and grew on PCL covered with Matrigel, with clearly visible cell outlines indicating normal morphology. Assessment of cell viability by the CCK-8 method showed that hiPSCs proliferated and grew on PCL scaffolds covered with Matrigel. After 6 d of culture, immunofluorescence showed that control group hiPSCs highly expressed the stem cell marker OCT4 but not myocardial markers cTnT or α-actin. In contrast, notable expression of myocardial markers cTnT and α-actin but not OCT4 occurred in the CDM3 group. hiPSCs can proliferate and grow on PCL scaffolds covered with Matrigel. Under the influence of CDM3, hiPSCs differentiated into cardiomyocyte-like cells, allowing the preliminary preparation of myocardial patches that can provide a better method for clinical treatment of myocardial infarction. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro, there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function.

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

Excessive or persistent inflammation incites cardiomyocytes necrosis by generating reactive oxygen species in myocardial infarction (MI). Hydrogen sulfide (H2S), a gaseous signal molecule, can quickly permeate cells and tissues, growing concerned for its cardioprotective effects. However, short resident time and strong side effects greatly restrict its application. Herein, a complex scaffold (AAB) is first developed to slowly release H2S for myocardial protection by integrating alginate modified with 2‐aminopyridine‐5‐thiocarboxamide (H2S donor) into albumin electrospun fibers. Next, a band‐aid like patch is constructed based on AAB (center) and nanocomposite scaffold which comprises albumin scaffold and black phosphorus nanosheets (BPNSs). With near‐infrared laser (808 nm), thermal energy generated by BPNSs can locally change the molecular structure of fibrous scaffold, thereby attaching patch to the myocardium. In this study, it is also demonstrated that AAB can enhance regenerative M2 macrophage and attenuate inflammatory polarization of macrophages via reduction in intracellular ROS. Eventually, this engineered cardiac patch can relieve inflammation and promote angiogenesis after MI, and thereby recover heart function, providing a promising therapeutic strategy for MI treatment. [ABSTRACT FROM AUTHOR]

Cell therapy is one of the promising approaches for cardiac repair, subsequently after infarction or injury. However, contemporary mesenchymal stromal/stem cell (MSCs) delivery strategies result in low retention and poor engraftment of donor cells, thus limiting the therapeutic efficacy. Here, we developed an engineered biomimetic cardiogel patch (EBCP) comprising of the native decellularized cardiac extracellular matrix (ECM) "cardiogel" and chitosan, leading to the efficient regeneration of injured myocardium. We also developed novel bio-adhesive that is capable of suture-free epicardial placement of EBCP to injured myocardium. We have illustrated the potential of the mussels-inspired bioadhesive system, which comprises gelatin catechol and partially oxidized chitosan, which relies on self-crosslinking capability, to promote wet adhesion. In vitro studies with isolated cardiogel promoted cell proliferation, adhesion, and migration while aiding cardiomyogenic differentiation. The EBCP's ability to protect cells from abrasion due to surrounding tissues in the myocardial infarction (MI) rat model makes it more desirable. Furthermore, the epicardial implantation of the EBCP loaded with MSCs improves the initial retention of cells and subsequent functional cardiac recovery with enhanced myocardial tissue restoration. Histological examination showed the presence of EBCP and infiltration of cells to the infarcted heart tissue. The fast and facile synthesis of bioadhesive and major therapeutic benefits of EBCP make it a potential candidate for recuperating the ailing heart. [Display omitted] [ABSTRACT FROM AUTHOR]

Ischemic diseases including myocardial infarction (MI) and limb ischemia are some of the greatest causes of morbidity and mortality worldwide. Cell therapy is a potential treatment but is usually limited by poor survival and retention of donor cells injected at the target site. Since much of the therapeutic effects occur via cell-secreted paracrine factors, including extracellular vesicles (EVs), we developed a porous material for cell encapsulation which would improve donor cell retention and survival, while allowing EV secretion. Human donor cardiac mesenchymal cells were used as a model therapeutic cell and the encapsulation system could sustain three-dimensional cell growth and secretion of therapeutic factors. Secretion of EVs and protective growth factors were increased by encapsulation, and secreted EVs had hypoxia-protective, pro-angiogenic activities in in vitro assays. In a mouse model of limb ischemia the implant improved angiogenesis and blood flow, and in an MI model the system preserved ejection fraction %. In both instances, the encapsulation system greatly extended donor cell retention and survival compared to directly injected cells. This system represents a promising therapy for ischemic diseases and could be adapted for treatment of other diseases in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

Cardiac tissue engineering has emerged as a promising strategy to treat infarcted cardiac tissues by replacing the injured region with an ex vivo fabricated functional cardiac patch. Nevertheless, integration of the transplanted patch with the host tissue is still a burden, limiting its clinical application. Here, a bi-functional, 3D bio-printed cardiac patch (CP) design is proposed, composed of a cell-laden compartment at its core and an extracellular vesicle (EV)-laden compartment at its shell for better integration of the CP with the host tissue. Alginate-based bioink solutions were developed for each compartment and characterized rheologically, examined for printability and their effect on residing cells or EVs. The resulting 3D bio-printed CP was examined for its mechanical stiffness, showing an elastic modulus between 4–5 kPa at day 1 post-printing, suitable for transplantation. Affinity binding of EVs to alginate sulfate (AlgS) was validated, exhibiting dissociation constant values similar to those of EVs with heparin. The incorporation of AlgS-EVs complexes within the shell bioink sustained EV release from the CP, with 88% cumulative release compared with 92% without AlgS by day 4. AlgS also prolonged the release profile by an additional 2 days, lasting 11 days overall. This CP design comprises great potential at promoting more efficient patch assimilation with the host. [ABSTRACT FROM AUTHOR]

The healthy human heart has special directional arrangement of cardiomyocytes and a unique electrical conduction system, which is critical for the maintenance of effective contractions. The precise arrangement of cardiomyocytes (CMs) along with conduction consistency between CMs is essential for enhancing the physiological accuracy of in vitro cardiac model systems. Here, we prepared aligned electrospun rGO/PLCL membranes using electrospinning technology to mimic the natural heart structure. The physical, chemical and biocompatible properties of the membranes were rigorously tested. We next assembled human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on electrospun rGO/PLCL membranes in order to construct a myocardial muscle patch. The conduction consistency of cardiomyocytes on the patches were carefully recorded. We found that cells cultivated on the electrospun rGO/PLCL fibers presented with an ordered and arranged structure, excellent mechanical properties, oxidation resistance and effective guidance. The addition of rGO was found to be beneficial for the maturation and synchronous electrical conductivity of hiPSC-CMs within the cardiac patch. This study verified the possibility of using conduction-consistent cardiac patches to enhance drug screening and disease modeling applications. Implementation of such a system could one day lead to in vivo cardiac repair applications.

Abstract Excessive or persistent inflammation incites cardiomyocytes necrosis by generating reactive oxygen species in myocardial infarction (MI). Hydrogen sulfide (H2S), a gaseous signal molecule, can quickly permeate cells and tissues, growing concerned for its cardioprotective effects. However, short resident time and strong side effects greatly restrict its application. Herein, a complex scaffold (AAB) is first developed to slowly release H2S for myocardial protection by integrating alginate modified with 2‐aminopyridine‐5‐thiocarboxamide (H2S donor) into albumin electrospun fibers. Next, a band‐aid like patch is constructed based on AAB (center) and nanocomposite scaffold which comprises albumin scaffold and black phosphorus nanosheets (BPNSs). With near‐infrared laser (808 nm), thermal energy generated by BPNSs can locally change the molecular structure of fibrous scaffold, thereby attaching patch to the myocardium. In this study, it is also demonstrated that AAB can enhance regenerative M2 macrophage and attenuate inflammatory polarization of macrophages via reduction in intracellular ROS. Eventually, this engineered cardiac patch can relieve inflammation and promote angiogenesis after MI, and thereby recover heart function, providing a promising therapeutic strategy for MI treatment.

Introduction: Abnormal electrical activity of the heart following myocardial infarction (MI) may lead to heart failure or sudden cardiac death. Graphene-based conductive hydrogels can simulate the microenvironment of myocardial tissue and improve cardiac function post-MI. However, existing methods for preparing graphene and its derivatives suffer from drawbacks such as low purity, complex processes, and unclear structures, which limiting their biological applications., Objectives: We propose an optimized synthetic route for synthesizing methoxytriethylene glycol-functionalized graphene (TEG-GR) with a defined structure. The aim of this study was to establish a novel self-adhesion conductive cardiac patch based on TEG-GR for protecting cardiac function after MI., Methods: We optimized π-extension polymerization (APEX) reaction to synthesize TEG-GR. TEG-GR was incorporated into dopamine-modified gelatin (GelDA) to construct conductive cardiac patch (TEG-GR/GelDA). We validated the function of TEG-GR/GelDA cardiac patch in rat models of MI, and explored the mechanism of TEG-GR/GelDA cardiac patch by RNA sequencing and molecular biology experiments., Results: Methoxytriethylene glycol side chain endows graphene with high electrical conductivity, low immunogenicity, and superior biological properties. In rats, transplantation of TEG-GR/GelDA cardiac patch onto the infarcted area of heart can more effectively enhance ejection fraction, attenuate collagen deposition, shorten QRS interval and increase vessel density at 28 days post-treatment, compared to non-conductive cardiac patch. Transcriptome analysis indicates that TEG-GR/GelDA cardiac patch can improve cardiac function by maintaining gap junction, promoting angiogenesis, and suppressing cardiomyocytes apoptosis., Conclusion: The precision synthesis of polymer with defined functional group expands the application of graphene in biomedical field, and the novel cardiac patch can be a promising candidate for treating MI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Engineered human cardiac tissues hold great promise for disease modeling, drug development, and regenerative therapy. For regenerative applications, successful engineered tissue engraftment in vivo requires rapid vascularization and blood perfusion post-implantation. In the present study, we engineered highly functional, vascularized cardiac tissues ("cardiopatches") by co-culturing human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) and endothelial cells (hiPSC-ECs) in optimized serum-free media. The vascularized cardiopatches displayed stable capillary networks over 4 weeks of culture, the longest reported in the field, while maintaining high contractile stress (>15 mN/mm 2 ) and fast conduction velocity (>20 cm/s). Robustness of the method was confirmed using two distinct hiPSC-EC sources. Upon implantation into dorsal-skinfold chambers in immunocompromised mice, in vitro vascularized cardiopatches exhibited improved angiogenesis compared to avascular implants. Significant lumenization of the engineered human vasculature and anastomosis with host mouse vessels yielded the formation of hybrid human-mouse capillaries and robust cardiopatch perfusion by blood. Moreover, compared to avascular tissues, the implanted vascularized cardiopatches exhibited significantly higher conduction velocity and Ca 2+ transient amplitude, longitudinally monitored in live mice for the first time. Overall, we demonstrate successful 4-week vascularization of engineered human cardiac tissues without loss of function in vitro, which promotes tissue functionality upon implantation in vivo. STATEMENT OF SIGNIFICANCE: Complex interactions between cardiac muscle fibers and surrounding capillaries are critical for everyday function of the heart. Tissue engineering is a powerful method to recreate functional cardiac muscle and its vascular network, which are both lost during a heart attack. Our study demonstrates in vitro engineering of dense capillary networks within highly functional engineered heart tissues that successfully maintain the structure, electrical, and mechanical function long-term. In mice, human capillaries from these engineered tissues integrate with host mouse capillaries to allow blood perfusion and support improved implant function. In the future, the developed vascularized engineered heart tissues will be used for in vitro studies of cardiac development and disease and as a potential regenerative therapy for heart attack., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Engineered hydrogel patches have shown promising therapeutic effects in the treatment of myocardial infarction (MI), especially anisotropic patches that mimic the characteristics of native myocardium have attracted widespread attention. However, it remains a great challenge to develop cardiac patches with long-range and orderly electrical conduction based on an effective, mild, and rapid strategy. Here, a multifunctional anisotropic cardiac patch is presented based on microfluidic manipulation. The anisotropic alginate-gelatin methacrylate hydrogel patches are easily and rapidly prepared through microfluidic focusing, ion-photocrosslinking, and parallel packing processes. The fluid-based anisotropic realization process does not involve complex machining and strong field stimulation and is compatible with the loading of macromolecular biological agents. The anisotropic hydrogel patch can mimic the anisotropy of the myocardium and guide the directional polarization of cardiomyocytes. In animal model experiments, it also exhibits significant effects in inhibiting ventricular remodeling, fibrosis, and enhancing cardiac function recovery after MI. These comprehensive features make the multifunctional hydrogel patch a promising candidate for cardiac tissue repair and future provide a new paradigm for expanding microfluidic technology to solve tissue engineering challenges., (© 2024 Wiley‐VCH GmbH.)

Melt electrowriting (MEW) is an electric-field-assisted additive biofabrication technique that has brought significant advancements to bioinspired scaffold design for soft tissue engineering and beyond. Owing to its targeted microfiber placement, MEW has become a powerful platform technology for the fabrication of in vitro disease models up to functional biohybrid constructs that are investigated in vivo to reach clinical translation soon. This work provides a concise overview of this rapidly evolving field by highlighting the key contributions of MEW to cardiovascular tissue engineering. Specifically, we i) pinpoint the methods to introduce microvascular networks in thick 3D constructs benefitting from (sacrificial) MEW microfibers, ii) report MEW-based concepts for small-diameter vascular grafts and stents, iii) showcase how contracting cardiac tissues can profit from the tunable structure-property relationship of MEW scaffolds, and iv) address how complete regenerative heart valves can be built on complex fiber scaffold architectures that recapitulate J-shaped tensile properties and tissue heterogeneity. Lastly, we touch on novel biomaterial advancements and discuss the technological challenges of MEW to unlock the full potential of this transformative technology., Competing Interests: ED-J-P is cofounder and director of CoraMetix Pty Ltd., which holds two patent applications related to 3D-printed heart valves. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission., (Copyright © 2024 Mueller, Mansi, De-Juan-Pardo and Mela.)

Summary: A biohybrid patch without cellular components was implanted over large infarcted areas in severely dilated hearts. Nonpatched animals were assigned to control or losartan therapy. Patch-implanted animals responded with better morphological and functional echocardiographic endpoints, which were more evident in a subgroup of animals with very low pre-treatment ejection fraction (

[Display omitted] • Developed a potential magnetostrictive cardiac patch, CoFe 2 O 4 -PVDF, for injured myocardium. • Enhanced piezoelectric effect due to the deformation of CoFe 2 O 4 and increased β phase and crystallinity of PVDF. • The magnetoelectric cues of CoFe 2 O 4 -PVDF synergistically positively influence on cardiomyocytes. • A new mechanism of magnetoelectric cues included steroid hormone biosynthesis, Na+ K+-ATPase and intracelluar Ca2+. Cardiac tissue engineering has great promise in the treatment of heart disease. Aiming to develop the novel magnetoelectric cardiac patch for improving the non-conduction of injured myocardium after myocardial infarction, the self-powered nanofiber sheet was electro-spun by doping magnetostrictive CoFe 2 O 4 in piezoelectric Poly (vinylidene fluoride) (PVDF). The piezoelectric ratios increased several folds with the doping of CoFe 2 O 4 due to the increased β phase and crystallinity of CoFe 2 O 4 -PVDF confirmed by experimental data. Molecular Dynamics and Finite Element Simulation demonstrated that non-β phase transformed to β phase of PVDF with doping CoFe 2 O 4 and the deformation of CoFe 2 O 4 enhanced the piezoelectric effect of PVDF, respectively. The proliferation and spread area of Doxorubicin-induced oxidative stress injured cardiomyocytes, H9c2 cells, were significantly improved under magnetoelectric cue compared with those without magnetoelectric cue when co-cultured with CoFe 2 O 4 -PVDF. Importantly, a new mechanism pathway of magnetoelectric cue on cardiomyocytes has been found, including up-regulating of steroid hormone biosynthesis, enhancing of sodium–potassium enzyme, and increasing of intracellular Ca2+, which would trigger the cardiomyocyte contraction to overcome the non-conduction of injured cardiomyocytes by RNA-seq transcriptome sequencing, Polymerase Chain Reaction and downstream expression analysis. Hence, this CoFe 2 O 4 -PVDF composite nanofiber sheet would be potentially used as the magnetoelectric cardiac patch to treat injured myocardium after myocardial infarction clinical. [ABSTRACT FROM AUTHOR]

Cardiac patch has been proposed as an alternative therapeutic tissue engineering strategy to treat damaged heart for patients who survive the acute myocardial infarction (MI). To that end, studies have focused on designing an ideal cardiac patch assisting myocardium to repair itself. The engineering of three dimensional (3 D) anisotropic knitted scaffolds could be an efficient and effective strategy for cardiac patches. Thus, the polyethylene terephthalate (PET) pile loop knit fabrics were fabricated as 3 D scaffolds, where the values of stiffness (Young's modulus) of the scaffolds were similar to those reported for the human myocardium. Anisotropic porous knitted scaffolds supported the adhesion and proliferation of murine C2C12 myoblasts cell line in vitro. Scaffolds with a high surface to volume ratio and porosity exhibited superior performance in terms of cell adhesion and proliferation. Furthermore, out of thirteen proinflammatory cytokines, the levels of three cytokines including IL-1α, IL-1β, and IL-11 were observed to be higher in cells seeded on scaffolds coated with fibronectin than those in related control groups. Thus, the proposed knitted structure can potentially be used for tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

Compared to cell therapy, where cells are injected into a defect region, the treatment of heart infarction with cells seeded in a vascularized scaffold bears advantages, such as an immediate nutrient supply or a controllable and persistent localization of cells. For this purpose, decellularized native tissues are a preferable choice as they provide an in vivo-like microenvironment. However, the quality of such scaffolds strongly depends on the decellularization process. Therefore, two protocols based on sodium dodecyl sulfate or sodium deoxycholate were tailored and optimized for the decellularization of a porcine heart. The obtained scaffolds were tested for their applicability to generate vascularized cardiac patches. Decellularization with sodium dodecyl sulfate was found to be more suitable and resulted in scaffolds with a low amount of DNA, a highly preserved extracellular matrix composition, and structure shown by GAG quantification and immunohistochemistry. After seeding human endothelial cells into the vasculature, a coagulation assay demonstrated the functionality of the endothelial cells to minimize the clotting of blood. Human-induced pluripotent-stem-cell-derived cardiomyocytes in co-culture with fibroblasts and mesenchymal stem cells transferred the scaffold into a vascularized cardiac patch spontaneously contracting with a frequency of 25.61 ± 5.99 beats/min for over 16 weeks. The customized decellularization protocol based on sodium dodecyl sulfate renders a step towards a preclinical evaluation of the scaffolds. [ABSTRACT FROM AUTHOR]

Despite a massive global preventative effort, heart failure remains the major cause of death globally. The number of patients requiring a heart transplant, the eventual last treatment option, far outnumbers the available donor hearts, leaving many to deteriorate or die on the transplant waiting list. Treating heart failure by transplanting a 3D bioprinted patient-specific cardiac patch to the infarcted region on the myocardium has been investigated as a potential future treatment. To date, several studies have created cardiac patches using 3D bioprinting; however, testing the concept is still at a pre-clinical stage. A handful of clinical studies have been conducted. However, moving from animal studies to human trials will require an increase in research in this area. This review covers key elements to the design of a patient-specific cardiac patch, divided into general areas of biological design and 3D modelling. It will make recommendations on incorporating anatomical considerations and high-definition motion data into the process of 3D-bioprinting a patient-specific cardiac patch. [ABSTRACT FROM AUTHOR]

Myocardial infarction caused by coronary artery obstruction results in the loss of heart muscle, which is subsequently replaced by scar tissue with limited therapeutic options. Cardiac patch based therapy has emerged as a promising strategy for the treatment of severe myocardial infarction. They are designed to be attached to the surface of the heart, that is, they are meant to "patch" the injured heart, thus restoring the damaged or failing myocardium locally through mechanical and regeneration support. The engineered three‐dimension cardiac patch is composed of biomaterial scaffolds with/without cells or inducible factors, which is typically manufactured by decellularize extracellular matrix, electrospinning, three‐dimension printing, hydrogels, or by stacking cell sheets. In this review, we outline the latest advances of the construction methods and beneficial effects of cardiac patches used in animal and clinical treatment of cardiovascular diseases, especially in myocardial infarction. We discuss the cell souring of cell‐based patches, the types of biomolecules for cell‐free patches, and their engineering methods. In addition, the method of implanting the cardiac patch to the injured heart is also described. Finally, we briefly outlook the future challenges and probable solutions in this area. [ABSTRACT FROM AUTHOR]

Abstract Myocardial infarction caused by coronary artery obstruction results in the loss of heart muscle, which is subsequently replaced by scar tissue with limited therapeutic options. Cardiac patch based therapy has emerged as a promising strategy for the treatment of severe myocardial infarction. They are designed to be attached to the surface of the heart, that is, they are meant to “patch” the injured heart, thus restoring the damaged or failing myocardium locally through mechanical and regeneration support. The engineered three‐dimension cardiac patch is composed of biomaterial scaffolds with/without cells or inducible factors, which is typically manufactured by decellularize extracellular matrix, electrospinning, three‐dimension printing, hydrogels, or by stacking cell sheets. In this review, we outline the latest advances of the construction methods and beneficial effects of cardiac patches used in animal and clinical treatment of cardiovascular diseases, especially in myocardial infarction. We discuss the cell souring of cell‐based patches, the types of biomolecules for cell‐free patches, and their engineering methods. In addition, the method of implanting the cardiac patch to the injured heart is also described. Finally, we briefly outlook the future challenges and probable solutions in this area.

Myocardial infarction (MI) is one of the fatal diseases in humans. Its incidence is constantly increasing annually all over the world. The problem is accompanied by the limited regenerative capacity of cardiomyocytes, yielding fibrous scar tissue formation. The propagation of electrical impulses in such tissue is severely hampered, negatively influencing the normal heart pumping function. Thus, reconstruction of the internal cardiac electrical connection is currently a major concern of myocardial repair. Conductive biomaterials with or without cell loading were extensively investigated to address this problem. This article introduces a detailed overview of the recent progress in conductive biomaterials and fabrication methods of conductive scaffolds for cardiac repair. After that, the advances in myocardial tissue construction in vitro by the restoration of intercellular communication and simulation of the dynamic electrophysiological environment are systematically reviewed. Furthermore, the latest trend in the study of cardiac repair in vivo using various conductive patches is summarized. Finally, we discuss the achievements and shortcomings of the existing conductive biomaterials and the properties of an ideal conductive patch for myocardial repair. We hope this review will help readers understand the importance and usefulness of conductive biomaterials in cardiac repair and inspire researchers to design and develop new conductive patches to meet the clinical requirements. After myocardial infarction, the infarcted myocardial area is gradually replaced by heterogeneous fibrous tissue with inferior conduction properties, resulting in arrhythmia and heart remodeling. Conductive biomaterials have been extensively adopted to solve the problem. Summarizing the relevant literature, this review presents an overview of the types and fabrication methods of conductive biomaterials, and focally discusses the recent advances in myocardial tissue construction in vitro and myocardial repair in vivo , which is rarely covered in previous reviews. As well, the deficiencies of the existing conductive patches and their construction strategies for myocardial repair are discussed as well as the improving directions. Confidently, the readers of this review would appreciate advantages and current limitations of conductive biomaterials/patches in cardiac repair. [Display omitted] [ABSTRACT FROM AUTHOR]

Additive manufacturing (AM) has increasing applications in medicine in recent times. This technology has emerged in cardiovascular medicine as an intelligent system for the improvement of medical devices, the preparation of patient-specific models, and the prototyping of grafts. This review traces the research and development in the production of surgical guides and synthetic grafts for cardiac and vascular applications over the last few years. It also traces the recent widespread use of 3D-printed specific-patient models for cardiovascular surgical interventions. A current view of AM strategies, materials and solutions to improve cardiovascular patient outcomes is also provided. [ABSTRACT FROM AUTHOR]