Design of a biomimetic electrospun scaffold for the in vitro modelling of cardiac fibrosis

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Affecting millions of people, Myocardial Infarction (MI) and Heart Failure (HF) are the major causes of death among CVDs. MI provokes the massive cardiomyocyte (CMs) loss in the infarcted zone followed by a progressive remodeling of left ventricle. CMs death triggers an inflammatory response followed by the proliferation of cardiac fibroblasts (CFs) in the ischemic region and their differentiation into cardiac myofibroblasts (MyoFs). These events lead to the extracellular matrix (ECM) components overdeposition and tissue stiffening, impairing cardiac function and resulting in cardiac fibrosis. Due to the limited regenerative capacity of native CMs, cardiac tissue cannot self-renew and restore its normal function after an injury. Currently heart functionality can only be restored by heart transplantation, which has been limited by the shortage of organ donors and potential side-effects post transplantation, such as implant rejection and infection. A variety of new therapies are being tested to regenerate infarcted myocardium and many approaches have been explored to engineer cardiac fibrosis in vitro. In vitro models can resemble specific physiological functions and be used in early stage research to investigate the efficiency and safety of therapeutic agents. They allow to replicate tissue specific architecture, although they do not mimic the complexity of the whole organ. The aim of this work was to design an in vitro model of human cardiac fibrotic tissue, through a bioartificial scaffold with tailored topographical cues, consisting of a synthetic polymer and a biomimetic coating. The effectiveness of the biomimetic surface functionalization was demonstrated by several physicochemical characterizations. Coating stability up to 7 days incubation in physiological media was also assessed. Preliminary cellular tests validated the effectiveness of the functionalized scaffolds in supporting cells adhesion, proliferation and activation. Once completely validated, the proposed in vitro model will be used for preclinical drug screening and as a platform to reproduce cardiac fibrosis. The work was part of BIORECAR ERC project (772168).