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Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-β promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair. [ABSTRACT FROM AUTHOR]

[Display omitted] • An oxygen releasing and antioxidant cardiac patch is developed. • The bilayered patch consist of antioxidant polyurethane, collagen and exosomes. • The patch promoted growth and survival of cardiac cells in in-vitro conditions. • The patch attenuated hypoxia, oxidative stress and promoted angiogenesis and heart repair after myocardial infarction in an in-vivo MI model. Constant oxygen supply is inevitable for cardiac tissue function and survival. Myocardial infarction (MI) leaves heart tissue in a state of oxygen deficiency, causing oxidative stress and irreversible death of cardiomyocytes. Although vital in treating MI, restoration of oxygen supply and attenuation of oxidative stress has not been successfully utilized as a therapeutic strategy. Herein, we developed and evaluated an oxygen releasing antioxidant nanofibrous bi-layered cardiac patch (PUAO-CPO-Collagen) supplemented with adipose derived stem cell exosomes (ADSC-EXO) to promote heart repair. Antioxidant polyurethane was synthesised and calcium peroxide (CPO) was incorporated as an oxygen releasing material. The bilayered cardiac patch consists of an oxygen releasing antioxidant polyurethane, electrospun over a porous collagen scaffold and supplemented with adipose derived stem cell exosomes. The patch demonstrated sustained release of oxygen and exosomes. Under in-vitro conditions, bilayered patch and ADSC exosomes illustrated proliferative, pro-angiogenic and pro-survival effect. In an in-vivo rat MI model, the bi-layered patch demonstrated enhanced cardiac function, reduced scar formation, significantly attenuating adverse cardiac remodelling through improved angiogenesis and decreased oxidative stress. Our study demonstrated an innovative and promising cell free biomaterial approach for delivering oxygen, promoting angiogenesis, and attenuating oxidative stress for enhanced heart regeneration after myocardial infarction. [ABSTRACT FROM AUTHOR]

Abstract: Cardiomyocytes in the body are subjected to cyclic mechanical strain induced by the rhythmic heart beating. In this study, we tested the hypothesis that cyclic strain promotes cardiomyogenesis of embryonic stem cell-derived cardiomyocytes (ESCs). ESCs cultured on elastic polymer [poly(lactide-co-caprolactone), PLCL] scaffolds subjected to cyclic strain in vitro displayed elevated cardiac gene expression compared to unstrained controls. Six weeks after implantation into infarcted rat myocardium, the elastic cardiac patches (ESC-seeded PLCL scaffolds) showed reduced fibrotic tissue formation, likely due to a combination of lower apoptotic activity, higher vascular endothelial growth factor (VEGF) expression, and more extensive angiogenesis in the strained versus unstrained control [ESC-seeded, non-elastic poly(lactide-co-glycolide) scaffolds] patches. Importantly, cardiac gene expression was upregulated in the elastic patches compared to control, with evidence for cardiomyocyte-specific microstructures including myofibrillar bundles and Z-lines. This study shows that the use of an elastic polymer scaffold designed to permit mechanical strain transduction as a cell transplantation vehicle significantly increases cardiomyogenesis of the implanted ESCs. [Copyright &y& Elsevier]

The development of minimally invasive cardiac patches, either as hemostatic dressing or treating myocardial infarction, is of clinical significance but remains a major challenge. Designing such patches often requires simultaneous consideration of several material attributes, including bioabsorption, non-toxicity, matching the mechanic properties of heart tissues, and working efficiently in wet and dynamic environments. Using genetically engineered multi-domain proteins, a printed bi-layer proteinaceous hydrogel patch for heart failure treatments is reported. The intrinsic self-healing nature of hydrogel materials physically enables seamless interfacial integration of two disparate hydrogel layers and functionally endows the cardiac patches with the combinatorial advantages of each layer. Leveraging the biocompatibility, structural stability, and tunable drug release properties of the bi-layer hydrogel, promising effects of hemostasis, fibrosis reduction, and heart function recovery on mice is demonstrated with two myocardium damage models. Moreover, this proteinaceous patch is proved biodegradable in vivo without any additive inflammations. In conclusion, this work introduces a promising new type of minimally invasive patch based on genetically modified double-layer protein gel for treating heart-related injuries or diseases., (© 2022 Wiley-VCH GmbH.)

Heart disease is one of the largest burdens to human health worldwide and has very limited therapeutic options. Engineered three-dimensional (3D) vascularized cardiac tissues have shown promise in rescuing cardiac function in diseased hearts and may serve as a whole organ replacement in the future. One of the major obstacles in reconstructing these thick myocardial tissues to a clinically applicable scale is the integration of functional vascular networks capable of providing oxygen and nutrients throughout whole engineered constructs. Without perfusion of oxygen and nutrient flow throughout the entire engineered tissue not only is tissue viability compromised, but also overall tissue functionality is lost. There are many supporting technologies and approaches that have been developed to create vascular networks such as 3D bioprinting, co-culturing hydrogels, and incorporation of soluble angiogenic factors. In this state-of-the-art review, we discuss some of the most current engineered vascular cardiac tissues reported in the literature and future directions in the field. Impact statement The field of cardiac tissue engineering is rapidly evolving and is now closer than ever to having engineered tissue models capable of predicting preclinical responses to therapeutics, modeling diseases, and being used as a means of rescuing cardiac function following injuries to the native myocardium. However, a major obstacle of engineering thick cardiac tissue remains to be the integration of functional vasculature. In this review, we highlight seminal and recently published works that have influenced and pushed the field of cardiac tissue engineering toward achieving vascularized functional tissues.

Polypyrrole (PPy) has been utilized in smart scaffolds to improve the functionality of the engineered cardiac tissue. Compared to the commonly used aqueous coating, here, PPy was blended into silk fibroin (SF) solution to electrospin conductive PPy-encapsulated SF nanofibers. Combinations of various SF concentrations (5%, 7%, and 12%) and different PPy-to-SF ratios (15:85, 30:70, and 40:60) were compared. PPy reduced the fiber diameter (0.431 ± 0.060 μm), better-mimicking the myocardium fibrils. Conductive mats with 7% SF showed the closest mechanical properties (1.437 ± 0.044 MPa) to the native myocardium; meanwhile, a PPy-to-SF ratio of 15:85 exhibited sufficient electrical conductivity for cardiomyocytes (CMs). In vitro studies using three different types of CM demonstrated that the hybrid mats support CM contraction. Primary neonatal rat CMs on the mat with a PPy-to-SF ratio of 15:85 were elongated and orientated anisotropically with locally organized sarcomeric striations. By contrast, human-induced pluripotent stem cell derived-CMs on the mat with a PPy-to-SF ratio of 30:70 exhibited the strongest contractions. Contraction synchrony was further improved by external stimulation. Taken together, these findings indicated the great potential of the PPy-encapsulated SF electrospun mat for cardiac tissue engineering. [ABSTRACT FROM AUTHOR]

Cardiac patch therapies promise to restore heart function and lower the risk of heart failure after heart attack. Fiber–matrix engineered tissue scaffolds have gained significant attention due to their tunable micro-structures, providing nonlinear mechanical properties similar to native anisotropic heart tissues. Mechanical properties of engineered scaffolds directly affect the stress fields generated inside and around the tissue scaffolds and have significant impact on the tissue functionality. Currently, biomedical cardiac patches are designed through experimentation and there exists a need for an accurate model that will allow micro-structural design optimization and analysis of effectiveness of the implanted patches. We have developed a three-dimensional large strain continuum model that can predict nonlinear, anisotropic mechanical response of engineered tissue scaffolds that have two orientation families of fibers inside a bulk hydrogel matrix. We have validated the predictive capability of our continuum model for the fiber–matrix composite using selected experiments and a suite of detailed finite element analysis that incorporated the micro-structural details of the composites. Comparing the continuum model predictions (1 element) against the representative volume micro-structural geometry finite element simulations (with greater than 4,00,000 elements), we show that the proposed model can accurately predict nonlinear mechanical behavior of highly anisotropic tissue scaffolds in both the longitudinal and transverse directions, as a function of the critical design parameters inter-fiber angle and fiber spacing. We show that the model can also capture native heart tissue's anisotropic large strain mechanical response. We implemented our model in the finite element software Abaqus by writing a user material subroutine UANISOHYPER and demonstrated its predictive abilities by conducting a full three-dimensional analysis of engineered tissue patch application on an infarcted heart. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is one of the leading causes of death worldwide. In recent years, regenerative medicine, tissue engineering and the development of new materials have become the focus of attention this field, and electrospinning technology to prepare nanofibrous materials for the treatment of cardiovascular diseases has attracted people's attention. Unlike previous reviews, this research enumerates the experimental methods and applications of electrospinning technology combined with nanofibrous materials in the directions of myocardial infarction repair, artificial heart valves, artificial blood vessels and cardiovascular patches from the perspective of cardiovascular surgery. In the end, this review also summarizes the limitations, unresolved technical challenges, and possible future directions of this technology for cardiovascular disease applications., Competing Interests: The 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., (Copyright © 2022 Huang, Huo, Cheng and Wang.)

Background: Damaged cardiac tissues could potentially be regenerated by transplanting bioengineered cardiac patches to the heart surface. To be fully paradigm-shifting, such patches may need to be transplanted using minimally invasive robotic cardiac surgery (not only traditional open surgery). Here, we present novel robotic designs, initial prototyping and a new surgical operation for instruments to transplant patches via robotic minimally invasive heart surgery. Methods: Robotic surgical instruments and automated control systems were designed, tested with simulation software and prototyped. Surgical proof-of-concept testing was performed on a pig cadaver. Results: Three robotic instrument designs were developed. The first (called "Claw" for the claw-like patch holder at the tip) operates on a rack and pinion mechanism. The second design ("Shell-Beak") uses adjustable folding plates and rods with a bevel gear mechanism. The third ("HeartStamp") utilizes a stamp platform protruding through an adjustable ring. For the HeartStamp, rods run through a cylindrical structure designed to fit a uniportal Video-Assisted Thorascopic Surgery (VATS) surgical port. Designed to work with or without a sterile sheath, the patch is pushed out by the stamp platform as it protrudes. Two instrument robotic control systems were designed, simulated in silico and one of these underwent early 'sizing and learning' prototyping as a proof-of-concept. To reflect real surgical conditions, surgery was run "live" and reported exactly (as-it-happened). We successfully picked up, transferred and released a patch onto the heart using the HeartStamp in a pig cadaver model. Conclusion: These world-first designs, early prototypes and a novel surgical operation pave the way for robotic instruments for automated keyhole patch transplantation to the heart. Our novel approach is presented for others to build upon free from restrictions or cost-potentially a significant moment in myocardial regeneration surgery which may open a therapeutic avenue for patients unfit for traditional open surgery., Competing Interests: The 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., (Copyright © 2022 Roche, Iyer, Nguyen, Mabroora, Dome, Sakr, Pawar, Lee, Wilson and Gentile.)

Myocardial infarction is one of the largest contributors to cardiovascular disease and reduces the ability of the heart to pump blood. One promising therapeutic approach to address the diminished function is the use of cardiac patches composed of biomaterial substrates and cardiac cells. These patches can be enhanced with the application of an auxetic design, which has a negative Poisson's ratio and can be modified to suit the mechanics of the infarct and surrounding cardiac tissue. Here, we examined multiple auxetic models (orthogonal missing rib and re-entrant honeycomb in two orientations) with tunable mechanical properties as a cardiac patch substrate. Further, we demonstrated that 3D printing based auxetic cardiac patches of varying thicknesses (0.2, 0.4, and 0.6 mm) composed of polycaprolactone and gelatin methacrylate can support induced pluripotent stem cell-derived cardiomyocyte function for 14-day culture. Taken together, this work shows the potential of cellularized auxetic cardiac patches as a suitable tissue engineering approach to treating cardiovascular disease.

Cardiovascular disease is one of the leading causes of mortality worldwide. Cardiac tissue engineering strategies focusing on biomaterial scaffolds incorporating cells and growth factors are emerging as highly promising for cardiac repair and regeneration. The use of stem cells within cardiac microengineered tissue constructs present an inherent ability to differentiate into cell types of the human heart. Stem cells derived from various tissues including bone marrow, dental pulp, adipose tissue and umbilical cord can be used for this purpose. Approaches ranging from stem cell injections, stem cell spheroids, cell encapsulation in a suitable hydrogel, use of prefabricated scaffold and bioprinting technology are at the forefront in the field of cardiac tissue engineering. The stem cell microenvironment plays a key role in the maintenance of stemness and/or differentiation into cardiac specific lineages. This review provides a detailed overview of the recent advances in microengineering of autologous stem cell-based tissue engineering platforms for the repair of damaged cardiac tissue. A particular emphasis is given to the roles played by the extracellular matrix (ECM) in regulating the physiological response of stem cells within cardiac tissue engineering platforms. [Display omitted] • Comprehensive review of the stem cell microenvironment in tissue engineering. • Outline of cardiac tissue engineering approaches targeting stem cell microenvironment. • Application and function of stem cell-based cardiac tissue engineering constructs. • The challenges and prospects of stem cell based cardiac tissue engineering. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are responsible for the major number of deaths around the world. Among these is heart failure after myocardial infarction whose latest therapeutic methods are limited to slowing the end-state progression. Numerous strategies have been developed to meet the increased demand for therapies regarding CVDs. This study aimed to establish a novel electrically conductive elastomer-based composite and assess its potential as a cardiac patch for myocardial tissue engineering. The electrically conductive carbon aerogels (CAs) used in this study were derived from waste paper as a cost-effective carbon source and they were combined with the biodegradable poly(glycerol-sebacate) (PGS) elastomer to obtain an electrically conductive cardiac patch material. To the best of our knowledge, this is the first report about the conductive composites obtained by the incorporation of CAs into PGS (CA-PGS). In this context, the incorporation of the CAs into the polymeric matrix significantly improved the elastic modulus (from 0.912 MPa for the pure PGS elastomer to 0.366 MPa for the CA-PGS) and the deformability (from 0.792 MPa for the pure PGS to 0.566 MPa for CA-PGS). Overall, the mechanical properties of the obtained structures were observed similar to the native myocardium. Furthermore, the addition of CAs made the obtained structures electrically conductive with a conductivity value of 65 × 10 -3 S m -1 which falls within the range previously recorded for human myocardium. The in vitro cytotoxicity assay with L929 murine fibroblast cells revealed that the CA-PGS composite did not have cytotoxic characteristics. On the other hand, the studies conducted with H9C2 rat cardiac myoblasts revealed that final structures were suitable for MTE applications according to the successes in cell adhesion, cell proliferation, and cell behavior., (© 2021 IOP Publishing Ltd.)

Cardiovascular diseases are the number one killer in the world. 1,2 Currently, there are no clinical treatments to regenerate damaged cardiac tissue, leaving patients to develop further life-threatening cardiac complications. Cardiac tissue has multiple functional demands including vascularization, contraction, and conduction that require many synergic components to properly work. Most of these functions are a direct result of the cardiac tissue structure and composition, and, for this reason, tissue engineering strongly proposed to develop substitute engineered heart tissues (EHTs). EHTs usually have combined pluripotent stem cells and supporting scaffolds with the final aim to repair or replace the damaged native tissue. However, as simple as this idea is, indeed, it resulted, after many attempts in the field, to be very challenging. Without design complexity, EHTs remain unable to mature fully and integrate into surrounding heart tissue resulting in minimal in vivo effects. 3 Lately, there has been a growing body of evidence that a complex, multifunctional approach through implementing scaffold designs, cellularization, and molecular release appears to be essential in the development of a functional cardiac EHTs. 4–6 This review covers the advancements in EHTs developments focusing on how to integrate contraction, conduction, and vascularization mimics and how combinations have resulted in improved designs thus warranting further investigation to develop a clinically applicable treatment. Optimizing cellular complexity, mechanical stimulation, electrical stimulation, matrix design, and vascularization through mimicking embryogenesis and development will result in full thickness, functional clinical patches for treating heart conditions. [Display omitted] • Current cell cardiac patches are limited in functionality in large models likely due to complexity. • Mimicking the embryogenesis through tissue complexity and developmental cues may improve maturation. • Vascularization, conduction, and contraction are important properties to optimize. • Many different types of stimulations improve maturation of cardiomyocytes. [ABSTRACT FROM AUTHOR]

Cardiac regenerative medicine faces big challenges such as a lack of adult cardiac stem cells, low turnover of mature cardiomyocytes, and difficulty in therapeutic delivery to the injured heart. The interaction of bioengineering and cardiac regenerative medicine offers innovative solutions to this field. For example, cell reprogramming technology has been applied by both direct and indirect routes to generate patient-specific cardiomyocytes. Various viral and non-viral vectors have been utilized for gene editing to intervene gene expression patterns during the cardiac remodeling process. Cell-derived protein factors, exosomes, and miRNAs have been isolated and delivered through engineered particles to overcome many innate limitations of live cell therapy. Protein decoration, antibody modification, and platelet membranes have been used for targeting and precision medicine. Cardiac patches have been used for transferring therapeutics with better retention and integration. Other technologies such as 3D printing and 3D culture have been used to create replaceable cardiac tissue. In this review, we discuss recent advancements in bioengineering and biotechnologies for cardiac regenerative medicine., Competing Interests: The 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., (Copyright © 2021 Chingale, Zhu, Cheng and Huang.)

Engineered heart tissues (EHTs) are regarded as being the most promising alternative to synthetic materials, and autologous mesenchymal stem cells (MSCs) are widely used as seeding cells. However, few studies have evaluated the feasibility of using MSCs from patients with cyanotic congenital heart disease (C-CHD) as seeding cells for EHTs, in comparison with cells from patients of acyanotic congenital heart disease (A-CHD). In the present study, we cultured MSCs from A-CHD and C-CHD patients in normoxia or hypoxia conditions, and compared their pro-angiogenic, anti-apoptotic and inflammation-modulatory potentials. In vivo , we seeded the cells into collagen patches conjugated with, or without, proangiogenic cytokines, which were used to repair the right ventricular outflow tract (RVOT) of rats. The in vitro results showed that C-CHD MSCs expressed higher levels of VEGFA and VEGFR 2 , and secreted more pro-angiogenic and anti-inflammatory cytokines under hypoxic conditions. On the other hand, apoptosis-related genes from C-CHD MSCs were modulated adaptably, converting these cells into an anti-apoptotic phenotype. In vivo studies demonstrated that in 4 weeks after RVOT reconstruction, cytokine-immobilized patches seeded with C-CHD MSCs exhibited preserved morphology, prolonged cell survival and enhanced angiogenesis compared to A-CHD MSCs. C-CHD MSCs that undergo "naturally hypoxic precondition" present a better cell source for EHTs, which would provide a promising individualized biomaterial for C-CHD patients. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) constitutes the first cause of morbidity and mortality in our life, so using highly conductive and elastic materials to produce an engineered cardiac patch is an effective way to improve the myocardium infarction area function. Here, shape memory polymers of the polyurethane/polyaniline/silicon oxide (PU/PANI/SiO 2 ) electrospinning sub-micron fiber patch were precisely produced in the case of the hydrogen bonding effect and interaction between the carboxyl groups to provide compatibility, phase mixing/miscibility, and stability. The sub-micron fiber patch prepared by our group has some remarkable characteristics, such as sub-micron fibers, 3D porous structure, special thickness to simulate the extracellular matrix (ECM), elastic deformation, good properties in conducting weak electrical signals, stability to maintain the whole structure, and self-adhesion. This sub-micron fiber material has been proven to be effective, easy, and reliable. Through precise design of the material system, structure regulation, and performance optimization, the aim is to produce a sub-micron fiber cardiac patch to simulate the myocardium ECM and improve conductive signal transduction for potential MI therapy.

Cardiovascular diseases are the number one killer in the world. 1 , 2 Currently, there are no clinical treatments to regenerate damaged cardiac tissue, leaving patients to develop further life-threatening cardiac complications. Cardiac tissue has multiple functional demands including vascularization, contraction, and conduction that require many synergic components to properly work. Most of these functions are a direct result of the cardiac tissue structure and composition, and, for this reason, tissue engineering strongly proposed to develop substitute engineered heart tissues (EHTs). EHTs usually have combined pluripotent stem cells and supporting scaffolds with the final aim to repair or replace the damaged native tissue. However, as simple as this idea is, indeed, it resulted, after many attempts in the field, to be very challenging. Without design complexity, EHTs remain unable to mature fully and integrate into surrounding heart tissue resulting in minimal in vivo effects. 3 Lately, there has been a growing body of evidence that a complex, multifunctional approach through implementing scaffold designs, cellularization, and molecular release appears to be essential in the development of a functional cardiac EHTs. 4-6 This review covers the advancements in EHTs developments focusing on how to integrate contraction, conduction, and vascularization mimics and how combinations have resulted in improved designs thus warranting further investigation to develop a clinically applicable treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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 (<35%). Patched animals also had smaller infarcts than both nonpatched groups. This simple approach could hold promise for clinical translation and be applied using minimally invasive procedures over the epicardium in a large set of patients to induce better ventricular remodeling, especially among those who are especially frail., Competing Interests: This work was funded by the Commonwealth of Pennsylvania, the RiMED Foundation, and the Italian Ministry of Education and Research (MIUR DOT1720429). Dr. Silveira-Filho was personally funded by FAPESP (São Paulo State Funding agency). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Tissue engineering combines principles of engineering and biology to generate living tissue equivalents for drug testing, disease modeling, and regenerative medicine. As techniques for reprogramming human somatic cells into induced pluripotent stem cells (iPSCs) and subsequently differentiating them into cardiomyocytes and other cardiac cells have become increasingly efficient, progress toward the development of engineered human cardiac muscle patch (hCMP) and heart tissue analogs has accelerated. A few pilot clinical studies in patients with post-infarction LV remodeling have been already approved. Conventional methods for hCMP fabrication include suspending cells within scaffolds, consisting of biocompatible materials, or growing two-dimensional sheets that can be stacked to form multilayered constructs. More recently, advanced technologies, such as micropatterning and three-dimensional bioprinting, have enabled fabrication of hCMP architectures at unprecedented spatiotemporal resolution. However, the studies working on various hCMP-based strategies for in vivo tissue repair face several major obstacles, including the inadequate scalability for clinical applications, poor integration and engraftment rate, and the lack of functional vasculature. Here, we review many of the recent advancements and key concerns in cardiac tissue engineering, focusing primarily on the production of hCMPs at clinical/industrial scales that are suitable for administration to patients with myocardial disease. The wide variety of cardiac cell types and sources that are applicable to hCMP biomanufacturing are elaborated. Finally, some of the key challenges remaining in the field and potential future directions to address these obstacles are discussed., Competing Interests: The 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., (Copyright © 2021 Wang, Serpooshan and Zhang.)

Engineered cardiac tissues hold tremendous promise for in vitro drug discovery, studies of heart development and disease, and therapeutic applications. Here, we describe a versatile "frame-hydrogel" methodology to generate engineered cardiac tissues with highly mature functional properties. This methodology has been successfully utilized with a variety of cell sources (neonatal rat ventricular myocytes, human and mouse pluripotent stem cell-derived cardiomyocytes) to generate tissues with diverse 3D geometries (patch, bundle, network) and levels of structural and functional anisotropy. Maturation of such engineered cardiac tissues is rapidly achieved without the need for exogenous electrical or mechanical stimulation or use of complex bioreactors, with tissues routinely reaching conduction velocities and specific forces of 25 cm/s and 20 mN/mm 2 , respectively, and forces per input cardiomyocyte of up to 12 nN. This method is reproducible and readily scalable to generate small tissues ideal for in vitro testing as well as tissues with large, clinically relevant dimensions.

Human induced pluripotent stem cells (hiPSCs) are among the most promising tools for regenerative myocardial therapy and in vitro modeling of cardiac disease; however, their full potential cannot be met without robust methods for differentiating them into cardiac-lineage cells. Here, we present novel protocols for generating hiPSC-derived cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) and for assembling them into a patch of human cardiac muscle (hCMP). The differentiation protocols can be completed in just a few weeks and are substantially more efficient than conventional methods, while the hCMP fabrication procedure produces a patch of clinically relevant size and incorporates a simple method for maturing the engineered tissue via mechanical stimulation. We also describe how the patch can be evaluated in a large-animal (swine) model of myocardial injury.

For the past decades, heart diseases remain the leading cause of death worldwide. In the adult mammalian heart, damaged cardiomyocytes will be replaced by non-contractile fibrotic scar tissues due to the poor regenerative ability of heart, causing heart failure subsequently. The development of tissue engineering has launched a new medical innovation for heart regeneration. As one of the most outstanding technology, cardiac patches hold the potential to restore cardiac function clinically. Consisted of two components: therapeutic ingredients and substrate scaffolds, the fabrication of cardiac patches requires both advanced bioactive molecules and biomaterials. In this review, we will present the most state-of-the-art cardiac patches and analysis their compositional details. The therapeutic ingredients will be discussed from cell sources to bioactive molecules. In the meanwhile, the recent advances to obtain scaffold biomaterials will be highlighted, including synthetic and natural materials. Also, we have focused on the challenges and potential strategies to fabricate clinically applicable cardiac patches., Competing Interests: The 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., (Copyright © 2020 Mei and Cheng.)

The vascularized cardiac patch strategy is promising for ischemic heart repair after myocardial infarction (MI), but current fabrication processes are quite complicated. Vascularized cardiac patches that can promote concurrent restoration of both the myocardium and vasculature at the injured site in a large animal model remain elusive. The safety and therapeutic benefits of a cardiac stromal cell patch integrated with engineered biomimetic microvessels (BMVs) were determined for treating MI. By leveraging a microfluidic method employing hydrodynamic focusing, we constructed the endothelialized microvessels and then encapsulated them together with therapeutic cardiosphere-derived stromal cells (CSCs) in a fibrin gel to generate a prevascularized cardiac stromal cell patch (BMV-CSC patch). We showed that BMV-CSC patch transplantation significantly promoted cardiac function, reduced scar size, increased viable myocardial tissue, promoted neovascularization, and suppressed inflammation in rat and porcine MI models, demonstrating enhanced therapeutic efficacy compared to conventional cardiac stromal cell patches. BMV-CSC patches did not increase renal and hepatic toxicity or exhibit immunogenicity. We noted a significant increase in endogenous progenitor cell recruitment to the peri-infarct region of the porcine hearts treated with BMV-CSC patch as compared to those that received control treatments. These findings establish the BMV-CSC patch as a novel engineered-tissue therapeutic for ischemic tissue repair.

Heart disease is the leading cause of death in the United States among both adults and infants. In adults, 5-year survival after a heart attack is <60%, and congenital heart defects are the top killer of liveborn infants. Problematically, the regenerative capacity of the heart is extremely limited, even in newborns. Furthermore, suitable donor hearts for transplant cannot meet the demand and require recipients to use immunosuppressants for life. Tissue engineered myocardium has the potential to replace dead or fibrotic heart tissue in adults and could also be used to permanently repair congenital heart defects in infants. In addition, engineering functional myocardium could facilitate the development of a whole bioartificial heart. Here, we review and compare in vitro and in situ myocardial tissue engineering strategies. In the context of this comparison, we consider three challenges that must be addressed in the engineering of myocardial tissue: recapitulation of myocardial architecture, vascularization of the tissue, and modulation of the immune system. In addition to reviewing and analyzing current progress, we recommend specific strategies for the generation of tissue engineered myocardial patches for heart regeneration and repair., (Copyright © 2020 Jarrell, Vanderslice, VeDepo and Jacot.)

Cardiac patches, three-dimensional (3D) constructs of polymer scaffold and heart muscle cells, have received widespread attention for regenerative therapy to repair damaged heart tissue. The implanted patches should mimic the micromechanical environment of native myocardium for effective integration and optimum mechanical function. In this study, we engineered compliant silicone scaffolds infused with cardiomyocytes (CMs) differentiated from human-induced pluripotent stem cells. Porous scaffolds are fabricated by extrusion 3D printing of room-temperature-vulcanized (RTV) silicone rubber. The stiffness and strength of scaffolds are tailored by designing a polymer strand arrangement during 3D printing. Single-strand scaffold design is found to display a tensile Young's modulus of ∼280 kPa, which is optimum for supporting CMs without impairing their contractility. Uniform distribution of cells in the scaffold is observed, ascribed to 3D migration facilitated by interconnected porous architecture. The patches demonstrated synchronized contraction 10 days after seeding scaffolds with CMs. Indentation measurements reveal that the contracting cell-scaffold patches display local moduli varying from ∼270 to 530 kPa, which covers the upper spectrum of the stiffness range displayed by the human heart. This study demonstrates the effectiveness of a porous 3D scaffold composed of flexible silicone rubber for CMs percolation, supporting a contractile activity, and mimicking native heart stiffness.

Recent advances in cardiac tissue engineering have shown that human induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured in a three-dimensional (3D) micro-environment exhibit superior physiological characteristics compared with their two-dimensional (2D) counterparts. These 3D cultured hiPSC-CMs have been used for drug testing as well as cardiac repair applications. However, the fabrication of a cardiac scaffold with optimal biomechanical properties and high biocompatibility remains a challenge. In our study, we fabricated an aligned polycaprolactone (PCL)-Gelatin coaxial nanofiber patch using electrospinning. The structural, chemical, and mechanical properties of the patch were assessed by scanning electron microscopy (SEM), immunocytochemistry (ICC), Fourier-transform infrared spectroscopy (FTIR)-spectroscopy, and tensile testing. hiPSC-CMs were cultured on the aligned coaxial patch for 2 weeks and their viability [lactate dehydrogenase (LDH assay)], morphology (SEM, ICC), and functionality [calcium cycling, multielectrode array (MEA)] were assessed. Furthermore, particle image velocimetry (PIV) and MEA were used to evaluate the cardiotoxicity and physiological functionality of the cells in response to cardiac drugs. Nanofibers patches were comprised of highly aligned core-shell fibers with an average diameter of 578 ± 184 nm. Acellular coaxial patches were significantly stiffer than gelatin alone with an ultimate tensile strength of 0.780 ± 0.098 MPa, but exhibited gelatin-like biocompatibility. Furthermore, hiPSC-CMs cultured on the surface of these aligned coaxial patches (3D cultures) were elongated and rod-shaped with well-organized sarcomeres, as observed by the expression of cardiac troponin-T and α-sarcomeric actinin. Additionally, hiPSC-CMs cultured on these coaxial patches formed a functional syncytium evidenced by the expression of connexin-43 (Cx-43) and synchronous calcium transients. Moreover, MEA analysis showed that the hiPSC-CMs cultured on aligned patches showed an improved response to cardiac drugs like Isoproterenol (ISO), Verapamil (VER), and E4031, compared to the corresponding 2D cultures. Overall, our results demonstrated that an aligned, coaxial 3D cardiac patch can be used for culturing of hiPSC-CMs. These biomimetic cardiac patches could further be used as a potential 3D in vitro model for "clinical trials in a dish" and for in vivo cardiac repair applications for treating myocardial infarction., (Copyright © 2020 Kumar, Sridharan, Palaniappan, Dougherty, Czirok, Isai, Mergaye, Angelos, Powell and Khan.)

Stroke and cardiovascular episodes are still some of the most common diseases worldwide, causing millions of deaths and costing billions of Euros to healthcare systems. The use of new biomaterials with enhanced biological and physical properties has opened the door to new approaches in cardiovascular applications. Elastin-based materials are biomaterials with some of the most promising properties. Indeed, these biomaterials have started to yield good results in cardiovascular and angiogenesis applications. In this review, we explore the latest trends in elastin-derived materials for cardiac regeneration and the different possibilities that are being explored by researchers to regenerate an infarcted muscle and restore its normal function. Elastin-based materials can be processed in different manners to create injectable systems or hydrogel scaffolds that can be applied by simple injection or as patches to cover the damaged area and regenerate it. Such materials have been applied to directly regenerate the damaged cardiac muscle and to create complex structures, such as heart valves or new bio-stents that could help to restore the normal function of the heart or to minimize damage after a stroke. We will discuss the possibilities that elastin-based materials offer in cardiac tissue engineering, either alone or in combination with other biomaterials, in order to illustrate the wide range of options that are being explored. Moreover, although tremendous advances have been achieved with such elastin-based materials, there is still room for new approaches that could trigger advances in cardiac tissue regeneration., (Copyright © 2020 Gonzalez de Torre, Alonso and Rodriguez-Cabello.)

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., Competing Interests: The authors declare no competing financial interest.

Ischemic heart disease (IHD) is one of the most common cardiovascular diseases and is the leading cause of death worldwide. Stem cell therapy is a promising strategy to promote cardiac regeneration and myocardial function recovery. Recently, the generation of human induced pluripotent cells (hiPSCs) and their differentiation into cardiomyocytes and vascular cells offer an unprecedented opportunity for the IHD treatment. This review briefly summarizes hiPSCs and their differentiation, and presents the recent advances in hiPSC injection, engineered cardiac patch fabrication, and the application of hiPSC derived extracellular vesicle. Current challenges and further perspectives are also discussed to understand current risks and concerns, identify potential solutions, and direct future clinical trials and applications., Competing Interests: Conflict of Interest None declared., (© 2020 Bin Duan, published by Sciendo.)

Heart failure (HF) after myocardial infarction (MI) due to blockage of coronary arteries is a major public health issue. MI results in massive loss of cardiac muscle due to ischemia. Unfortunately, the adult mammalian myocardium presents a low regenerative potential, leading to two main responses to injury: fibrotic scar formation and hypertrophic remodeling. To date, complete heart transplantation remains the only clinical option to restore heart function. In the last two decades, tissue engineering has emerged as a promising approach to promote cardiac regeneration. Tissue engineering aims to target processes associated with MI, including cardiomyogenesis, modulation of extracellular matrix (ECM) remodeling, and fibrosis. Tissue engineering dogmas suggest the utilization and combination of two key components: bioactive molecules and biomaterials. This chapter will present current therapeutic applications of biomaterials in cardiac regeneration and the challenges still faced ahead. The following biomaterial-based approaches will be discussed: Nano-carriers for cardiac regeneration-inducing biomolecules; corresponding matrices for their controlled release; injectable hydrogels for cell delivery and cardiac patches. The concept of combining cardiac patches with controlled release matrices will be introduced, presenting a promising strategy to promote endogenous cardiac regeneration., (Copyright © 2020 Bar and Cohen.)

Graphene based nanomaterials are promising candidates for cardiac tissue engineering due to the excellent electrical and mechanical properties and the robust surface chemistry. This research was designed to investigate the physicochemical and biological effects of increasing concentration of reduced graphene oxide (rGO) coating on collagen (Col) scaffolds as well as their antibacterial properties. Enhanced GO coating content to 400 μg/ml and its reduction showed improvement of HUVECs viability, however, following reduction of more GO concentration, decreased cell viability was observed. Compared with the Col counterpart, electroactive containing rGO scaffolds upregulated cardiac gene expression involve in electrical coupling (Cx43), muscle contraction and relaxation (troponin-T) and cytoskeleton alignment (actinin-4) after 7 days even without external electrical stimulation. rGO coating significantly improved mechanical properties and the electroactivity of the Col scaffolds reaching to 1100 ± 31 kPa and 4 × 10−4 ± 1.20 S/m for GO concentration of 800 μg/ml, respectively. Also, the antibacterial properties of Col-rGO-400 scaffolds against Escherichia coli , Staphylococcus aureus and Streptococcus pyogenes were confirmed by culture and FESEM observation. Taken together, the results indicated that rGO coating presents promising properties to Col scaffolds providing a desirable micro environment for cardiomyocytes coupling and gene upregulation as well as antibacterial activities for cardiac patch application. Unlabelled Image • Electroactive scaffolds provide a desirable micro environment for cardiomyocytes • rGO coating exhibit antibacterial properties. • Increasing rGO coating concentration improve the elastic modulus of the scaffold. • rGO could be cytotoxic depending on its concentration. [ABSTRACT FROM AUTHOR]

Electrospun fibers based on combinations of poly(ε-caprolactone) (PCL) and poly(glycerol sebacate) (PGS) have been studied for applications in cardiac tissue engineering. The aim of the present study is to demonstrate the fabrication of PCL and PGS prepolymer or mildly crosslinked PGS by electrospinning using less toxic solvents, like acetic acid, as opposed to conventional solvents such as chloroform or dichloromethane. The morphological and physiochemical properties and degradation susceptibility of the fiber mats were determined. A cell study using ST2 cells was performed to assess cytocompatibility. Neat PCL and PCL/PGS blends showed defect-free microstructures, whereby the average fiber diameter increased with the addition of PGS (0.8 ± 0.3 μm and 1.3 ± 0.7 μm, respectively). The mechanical properties were tested at 23 °C and 37 °C and showed higher values compared to native human myocardium. Degradation studies revealed a fast PGS degradation but the mildly cross-linked PGS resulted in acidification of the degradation medium. The biocompatibility was significantly increased when the samples were disinfected in 70% v/v ethanol in comparison to ultra-violet light disinfection. PCL/PGS fibers fabricated with acetic acid proved to be potentially suitable for application in cardiac tissue engineering based on their mechanical properties and biodegradability. Unlabelled Image • Benign electrospinning of poly(ε-caprolactone)(PCL)/poly(glycerol sebacate)(PGS) • Homogenous and defect-free PCL/PGS fiber mats were achieved using acetic acid. • PGS increased the degradation process in the blend fiber mats. • Ethanol disinfection improved cell viability of blend compared to ultraviolet light. [ABSTRACT FROM AUTHOR]

One of the leading causes of death worldwide is heart failure. Despite advances in the treatment and prevention of heart failure, the number of affected patients continues to increase. We have recently developed 3D-bioprinted biomaterial-free cardiac tissue that has the potential to improve cardiac function. This study aims to evaluate the in vivo regenerative potential of these 3D-bioprinted cardiac patches. The cardiac patches were generated using 3D-bioprinting technology in conjunction with cellular spheroids created from a coculture of human-induced pluripotent stem cell-derived cardiomyocytes, fibroblasts, and endothelial cells. Once printed and cultured, the cardiac patches were implanted into a rat myocardial infarction model (n = 6). A control group (n = 6) without the implantation of cardiac tissue patches was used for comparison. The potential for regeneration was measured 4 weeks after the surgery with histology and echocardiography. 4 weeks after surgery, the survival rates were 100% and 83% in the experimental and the control group, respectively. In the cardiac patch group, the average vessel counts within the infarcted area were higher than those within the control group. The scar area in the cardiac patch group was significantly smaller than that in the control group. (Figure S1) Echocardiography showed a trend of improvement of cardiac function for the experimental group, and this trend correlated with increased patch production of extracellular vesicles. 3D-bioprinted cardiac patches have the potential to improve the regeneration of cardiac tissue and promote angiogenesis in the infarcted tissues and reduce the scar tissue formation., (© 2019 John Wiley & Sons, Ltd.)

The protection from ischaemia-reperfusion-associated myocardial infarction worsening remains a big challenge. We produced a bioartificial 3D cardiac patch with cardioinductive properties on stem cells. Its multilayer structure was functionalised with clinically relevant doses of adenosine. We report here the first study on the potential of these cardiac patches in the controlled delivery of adenosine into the in vivo ischaemic-reperfused pig heart. A Fourier transform infrared chemical imaging approach allowed us to perform a characterisation, complementary to the histological and biochemical analyses on myocardial samples after in vivo patch implantation, increasing the number of investigations and results on the restricted number of pigs (n = 4) employed in this feasibility step. In vitro tests suggested that adenosine was completely released by a functionalised patch, a data that was confirmed in vivo after 24 hr from patch implantation. Moreover, the adenosine-loaded patch enabled a targeted delivery of the drug to the ischaemic-reperfused area of the heart, as highlighted by the activation of the pro-survival signalling reperfusion injury salvage kinases pathway. At 3 months, though limited to one animal, the used methods provided a picture of a tissue in dynamic conditions, associated to the biosynthesis of new collagen and to a non-fibrotic outcome of the healing process underway. The synergistic effect between the functionalised 3D cardiac patch and adenosine cardioprotection might represent a promising innovation in the treatment of reperfusion injury. As this is a feasibility study, the clinical implications of our findings will require further in vivo investigation on larger numbers of ischaemic-reperfused pig hearts., (© 2019 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Mesenchymal stromal/stem cell (MSC)-based therapy is a promising approach for the treatment of heart failure. However, current MSC-delivery methods result in poor donor cell engraftment, limiting the therapeutic efficacy. To address this issue, we introduce here a novel technique, epicardial placement of bi-layered, adhesive dressings incorporating MSCs (MSC-dressing), which can be easily fabricated from a fibrin sealant film and MSC suspension at the site of treatment. The inner layer of the MSC dressing, an MSC-fibrin complex, promptly and firmly adheres to the heart surface without sutures or extra glues. We revealed that fibrin improves the potential of integrated MSCs through amplifying their tissue-repair abilities and activating the Akt/PI3K self-protection pathway. Outer collagen-sheets protect the MSC-fibrin complex from abrasion by surrounding tissues and also facilitates easy handling. As such, the MSC-dressing technique not only improves initial retention and subsequent maintenance of donor MSCs but also augment MSC's reparative functions. As a result, this technique results in enhanced cardiac function recovery with improved myocardial tissue repair in a rat ischemic cardiomyopathy model, compared to the current method. Dose-dependent therapeutic effects by this therapy is also exhibited. This user-friendly, highly-effective bioengineering technique will contribute to future success of MSC-based therapy., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Impact Statement: This work explores placental tissue as a cell source for fabrication of tissue-engineered surgical patches for myocardial repair of congenital heart defects. This study demonstrates promising findings for the clinically driven evaluation of the cell source as defined by potential cardiac benefit, compatibility, cell source availability, and implant deliverability. It documents methods for the isolation of mesenchymal stem cells from human placental amnion and chorion tissues, characterization of these cells, and eventual cell sheet growth that can be leveraged going forward for patch fabrication. It establishes support to continue pursuing the placenta as a valuable cell source for myocardial repair.

Congenital heart disease is the number one cause of birth defect-related death because it often leads to right ventricular heart failure (RVHF). One promising avenue to combat this RVHF is the use of cardiac patches composed of stem cells and scaffolds. Herein, we demonstrate a reparative cardiac patch by combining neonatal or child c-kit +   progenitor cells (CPCs) with a scaffold composed of electrospun polycaprolactone nanofibers. We examined different parameters of the patch, including the alignment, composition, and surface properties of the nanofibers, as well as the age of the CPCs. The patch based on uniaxially aligned nanofibers successfully aligned the CPCs. With the inclusion of gelatin in the nanofiber matrix and/or coating of fibronectin on the surface of the nanofibers, the metabolism of both neonatal and child CPCs was generally enhanced. The conditioned media collected from both patches based on aligned and random nanofibers could reduce the fibrotic gene expression in rat cardiac fibroblasts, following stimulation with transforming growth factor β. Furthermore, the conditioned media collected from the nanofiber-based patches could lead to the formation of tubes of human umbilical vein endothelial cells, indicating the pro-angiogenic capability of the patch. Taken together, the electrospun nanofiber-based patches are a suitable delivery vehicle for CPCs and can confer reparative benefit through anti-fibrotic and pro-angiogenic paracrine signaling.

Right ventricular failure (RVF) is a common cause of death in patients suffering from pulmonary arterial hypertension (PAH). The current treatment for PAH only moderately improves symptoms, and RVF ultimately occurs. Therefore, it is necessary to develop new treatment strategies to protect against right ventricle (RV) maladaptation despite PAH progression. In this study, we hypothesize that local mesenchymal stem cell (MSC) delivery via a novel bioscaffold can improve RV function despite persistent PAH. To test our hypothesis, we induced PAH in adult rats with SU5416 and chronic hypoxia exposure; treated with rat MSCs delivered by intravenous injection, intramyocardial injection, or epicardial placement of a bioscaffold; and then examined treatment effectiveness by in vivo pressure-volume measurement, echocardiography, histology, and immunohistochemistry. Our results showed that compared with other treatment groups, only the MSC-seeded bioscaffold group resulted in RV functional improvement, including restored stroke volume, cardiac output, and improved stroke work. Diastolic function indicated by end-diastolic pressure-volume relationship was improved by the local MSC treatments or bioscaffold alone. Cardiomyocyte hypertrophy and RV fibrosis were both reduced, and von Willebrand factor expression was restored by the MSC-seeded bioscaffold treatment. Overall, our study suggests a potential new regenerative therapy to rescue the pressure-overload failing RV with persistent pulmonary vascular disease, which may improve quality of life and/or survival of PAH patients. NEW & NOTEWORTHY We explored the effects of mesenchymal stem cell-seeded bioscaffold on right ventricles (RVs) of rats with established pulmonary arterial hypertension (PAH). Some beneficial effects were observed despite persistent PAH, suggesting that this may be a new therapy for RV to improve quality of life and/or survival of PAH patients.

Aim: The aim of this study was to evaluate the efficacy of tissue-engineered amniotic membrane (AM) in the treatment of myocardial infarction lesions., Materials & Methods: 20 rats were subjected to coronary arterial ligation in order to induce myocardial infarction injury. Decellularized human AMs were seeded with 2 × 10 5 adipose-derived mesenchymal stem cells and were implanted in the infarcted hearts., Results & Conclusion: Histological and immunohistochemical evaluations indicated the regeneration of cardiomyocytes and reduction of inflammation and fibrosis in the patch-implanted group compared with a control group, 14 days after the surgery. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling assay was suggestive for apoptosis reduction in the patch-implanted specimens. This study suggested that human AM can be developed into a novel treatment for treating postmyocardial infarction.