Development of a biological scaffold from adult human skin for cardiovascular repair and regeneration

Cardiovascular diseases (CVDs) are still the leading cause of death and disabilities globally. Among CVDs, ischemic heart disease (IHD) has remained the leading cause of death worldwide in the last 16 years. IHD is caused by a sudden blockage of blood flow through coronary arteries that prevents the supply of oxygen and nutrients to the region of myocardium fed by the affected vessels. This condition causes the necrosis of the myocardium that is followed by a reparative process that starts from the infarcted area, but then involves, at later stages, also the uninjured myocardium, causing progressive fibrosis that may lead eventually to heart failure. Unfortunately, there is no cure for IHD and therapy can at best control symptoms and prevent a second ischemic event. The induction of post-infarction cardiac regeneration by the means of three factors, cells, scaffold and signals, is currently the target of cardiac tissue engineering. However, the field is still at its infancy and all three factors are yet to be defined. Since the ECM is the naturally occurring scaffold loaded with uncountable biological and mechanical signals, we aimed at obtaining and characterizing a biological three-dimensional scaffold for cardiac repair and regeneration from the adult human skin. Our results provided evidence that the scaffold of decellularized human skin (d-HuSk) was acellular and had a preserved architecture, retained components of the ECM that are also typical of cardiac matrix and are critical for cardiac functions and mechanical properties of the ECM, like collagen, fibronectin, laminin, tenascin, elastin and GAGs. Additionally, growth factors stored in d-HuSk matrix were similar to those found in cardiac matrix and, as similar were the signals, similar were the effects of d-HuSk and cardiac matrix on human cardiac progenitor cells (hCPCs). Indeed, as emerged from cytocompatibility study, the environment offered by d-HuSk did not differ from the cardiac native one in supporting engraftment and survival of hCPCs. Furthermore, d-HuSk attracted hCPCs from the cardiac native matrix and sustained their differentiation and differentiation towards cardiac myocytes. Therefore, d-HuSk is a biological scaffold that is easily obtained and might be used as an autograft. It shares to a large extent the composition of the cardiac native matrix, exerts on hCPCs similar effects in vitro and is also capable of stimulating their mobilization and engraftment. Overall, d-HuSk fulfills the key requirements needed for a scaffold to warrant its use in tissue engineering and, then, holds great promise as substitute for cardiac environment. Additionally, consisting of ECM proteins and being a storage of growth factors, d-HuSk might alone provide two of the three pillars of tissue engineering, namely the scaffold and the signals, and might be exploited as stand-alone scaffold to boost cardiac regeneration by recruiting resident cardiac progenitor cells, or as a cellularized scaffold by preparing a cardiac engineered tissue in vitro with the cell population of choice.