I-CARE: implantable decellularized-based cardiac patch for cardiac tissue repair

Introduction: Cardiovascular diseases account for 32% of the global deaths, comprising different pathologies related to heart failure. [1] The heart self-regeneration is limited, which is associated to the highest mortality and morbidity rates of cardiovascular diseases. The incapacity of endogenous regeneration reduces therapeutic approaches to the relief of symptoms rather than restoring the proper function of the heart. The developed strategies to guide the regeneration of cardiac tissue lacks on biocompatibility, cell homing and engraftment. [2] The I-CARE project intends to develop an ECM-based implantable cardiac patch to promote in-situ the self-regeneration of myocardial tissue. Objectives: The I-CARE project proposes the use of Supercritical carbon dioxide (scCO2) technology to decellularize cardiac tissue. The decellularized matrix (dECM) will be further used to develop biocompatible patches with chemical and physical features able to support the recellularization with cardiomyocytes. The decellularized cardiac patch will stimulate in- situ cardiomyocyte contractility and support the regeneration of myocardial tissue. In addition, the dECM matrix will be manipulated to produce printable and injectable hydrogels, able to support the co- culture of cardiomyocytes (CMs) and mesenchymal stem cells (MSCs). Conclusions: The I-CARE project focuses on recovering damaged cardiac through the application of dECM-based patch, recellularized with viable cardiomyocytes. In addition, the dECM cardiac patch encapsulated with MSCs would benefit of its paracrine effects, including the anti-apoptosis, anti-inflammation effects, neovascularization features and the inhibition of fibrosis and; the perfectly aligned CMs capable of remuscularize the infarcted injury, electromechanical integration and synchronous activation with host myocardium. The proposed research is ambitious, and it is expected to generate relevant knowledge related to the behaviour of CMs on the developed cardiac ECM-mimic patches and, the crosstalk between CMs and MSCs towards cardiac tissue regeneration.