Heart regeneration: 20 years of progress and renewed optimism.

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.

A Bi‐Layer Hydrogel Cardiac Patch Made of Recombinant Functional Proteins

Bioprinting aims to provide new avenues for regenerating damaged human tissues through the controlled printing of live cells and biocompatible materials that can function therapeutically. Polymeric hydrogels are commonly investigated ink materials for 3D and 4D bioprinting applications, as they can contain intrinsic properties relative to those of the native tissue extracellular matrix and can be printed to produce scaffolds of hierarchical organization. The incorporation of nanoscale material additives, such as nanoparticles, to the bulk of inks, has allowed for significant tunability of the mechanical, biological, structural, and physicochemical material properties during and after printing. The modulatory and biological effects of nanoparticles as bioink additives can derive from their shape, size, surface chemistry, concentration, and/or material source, making many configurations of nanoparticle additives of high interest to be thoroughly investigated for the improved design of bioactive tissue engineering constructs. This paper aims to review the incorporation of nanoparticles, as well as other nanoscale additive materials, to printable bioinks for tissue engineering applications, specifically bone, cartilage, dental, and cardiovascular tissues. An overview of the various bioinks and their classifications will be discussed with emphasis on cellular and mechanical material interactions, as well the various bioink formulation methodologies for 3D and 4D bioprinting techniques. The current advances and limitations within the field will be highlighted.

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Nanocomposite Bioprinting for Tissue Engineering Applications

Cardiovascular diseases (CVD), such as myocardial infarction (MI), constitute one of the world’s leading causes of annual deaths. This cardiomyopathy generates a tissue scar with poor anatomical properties and cell necrosis that can lead to heart failure. Necrotic tissue repair is required through pharmaceutical or surgical treatments to avoid such loss, which has associated adverse collateral effects. However, to recover the infarcted myocardial tissue, biopolymer-based scaffolds are used as safer alternative treatments with fewer side effects due to their biocompatibility, chemical adaptability and biodegradability. For this reason, a systematic review of the literature from the last five years on the production and application of chitosan scaffolds for the reconstructive engineering of myocardial tissue was carried out. Seventy-five records were included for review using the “preferred reporting items for systematic reviews and meta-analyses” data collection strategy. It was observed that the chitosan scaffolds have a remarkable capacity for restoring the essential functions of the heart through the mimicry of its physiological environment and with a controlled porosity that allows for the exchange of nutrients, the improvement of the electrical conductivity and the stimulation of cell differentiation of the stem cells. In addition, the chitosan scaffolds can significantly improve angiogenesis in the infarcted tissue by stimulating the production of the glycoprotein receptors of the vascular endothelial growth factor (VEGF) family. Therefore, the possible mechanisms of action of the chitosan scaffolds on cardiomyocytes and stem cells were analyzed. For all the advantages observed, it is considered that the treatment of MI with the chitosan scaffolds is promising, showing multiple advantages within the regenerative therapies of CVD.

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Chitosan-Based Scaffolds for the Treatment of Myocardial Infarction: A Systematic Review

We are pleased to present this Special Issue of Cells, entitled 'Feature Papers in Stem Cells' [...].

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Fundamental and Applied Advances in Stem Cell Therapeutic Research

Myocardium Infarction (MI) is one of the foremost cardiovascular diseases (CVDs) causing death worldwide, and its case numbers are expected to continuously increase in the coming years. Pharmacological interventions have not been at the forefront in ameliorating MI-related morbidity and mortality. Stem cell-based tissue engineering approaches have been extensively explored for their regenerative potential in the infarcted myocardium. Recent studies on microfluidic devices employing stem cells under laboratory set-up have revealed meticulous events pertaining to the pathophysiology of MI occurring at the infarcted site. This discovery also underpins the appropriate conditions in the niche for differentiating stem cells into mature cardiomyocyte-like cells and leads to engineering of the scaffold via mimicking of native cardiac physiological conditions. However, the mode of stem cell-loaded engineered scaffolds delivered to the site of infarction is still a challenging mission, and yet to be translated to the clinical setting. In this review, we have elucidated the various strategies developed using a hydrogel-based system both as encapsulated stem cells and as biocompatible patches loaded with cells and applied at the site of infarction.

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Rohit Gundamaraju

Papers

Recent Advances in Cardiac Tissue Engineering for the Management of Myocardium Infarction.