Myocardial infarction is caused by the obstruction of coronary arteries, resulting in the death of approximately 1 billion cardiomyocytes in the left ventricle within a few hours. Additionally, myocardial infarction causes acute inflammation and degradation of the cardiac extracellular matrix, in turn, resulting in the formation of a fibrotic scar. Fibrotic tissue is mechanically stiffer than healthy cardiac tissue, it is mainly populated by cardiac fibroblasts and it lacks beating cardiomyocytes. Cardiac scars may undergo continuous remodeling, leading to left ventricle dilation and progressive congestive heart failure, which is the current leading cause of mortality and morbidity in the industrialized world. The only standard therapy addressing the irreversible loss of functional cardiomyocytes is heart transplantation. This option, however, is limited by donor scarcity and the need for life-long recipient immunosuppression. Thus, an ideal cardiac regenerative medicine strategy should replace lost cardiomyocytes and recover functional myocardial contractility.

To this purpose, cell-based regenerative therapies, biomaterials and tissue engineered scaffolds/patches are under investigation. Currently, the success of such therapies is limited by the poor grafting, survival and integration of implanted cells in the infarcted area, and the limited endogenous regenerative potential of the adult heart. Hence, the regeneration of a damaged heart remains a major clinical challenge with deep social and economic impact. Direct reprogramming approaches, able to directly convert cardiac fibroblasts into induced cardiomyocytes, have emerged in the last years and offer an intriguing new possibility for myocardial regeneration. However, despite the excitement surrounding the potentiality of direct cell reprogramming on cardiac regeneration, the approach is still rather immature and inefficient. In early studies, reprogramming efficiency was low, mainly employed viral vectors, and generated predominantly immature, partially reprogrammed and non-beating cardiomyocytes . New emerging studies are now making use of small molecules or microRNAs for direct cardiac reprogramming, paving the way towards safer and more effective strategies for cardiac regeneration. Additionally, parallel studies are investigating a combination of microRNAs able to induce cardiomyocyte proliferation.

This Research Topic is aimed at the publication of interdisciplinary studies on advanced therapies for cardiac regeneration. Through a collection of original papers and review articles, this Research Topic aims to collect the latest state-of-the-art ideas, concepts, findings, achievements and future directions of this field. The Research Topic hopes to promote awareness of multidisciplinary studies, thereby aspiring to bridge the gap between fields such as medicine, material sciences, biomechanics, pharmacy and engineering for research collaboration to address cardiac regeneration. Clinicians and researchers are invited to contribute with their original evidence-based articles, as well as critical literature review manuscripts, summarizing the most recent and exciting innovative developments.

Potential topics include, but are not limited to, the following:
• Basic studies on cell behavior in pathological and healthy cardiac tissue
• Biomaterials in cell differentiation and/or reprogramming
• Scaffolds for cardiac tissue engineering
• Cell therapies for cardiac regeneration
• Injectable hydrogels for cardiac tissue engineering
• Direct cardiac reprogramming
• In vitro tissue-engineering models of healthy and pathological cardiac tissue
• Nanomedicine for gene therapy in cardiac regeneration
• Drug release for cardiac regeneration
• New microfluidic platforms for cardiac differentiation/reprogramming
• Microfluidic models of cardiac tissue

The Research Topic is organized in the framework of the project BIORECAR (grant number: 772168; http://www.biorecar.polito.it/index.html)

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