Cardiac Extracellular Matrix-Fibrin Hydrogel Scaffolds with Tunable Properties for Cardiac Tissue Engineering

Introduction: Heart disease is currently the leading cause of death worldwide [1]. The majority of available therapies are geared toward slowing down the progression of heart disease and not toward restoring the contractile function of the affected tissues [2]. Extracellular matrix (ECM) obtained from decellularized cardiac tissue is a promising scaffold material that can be utilized to repair damaged areas of the myocardium by promoting vascularization and potentially the differentiation of cardiac stem cells [3-5]. Solubilizing ECM and reforming it into a hydrogel with tunable properties would allow for the development of 3D biomaterials that better mimic the native cardiac tissue. However, in its solubilized form, ECM lacks sufficient mechanical properties that enable it to form stable hydrogels in vitro. Although crosslinking can be used to improve the stiffness of ECM gels [3], the most effective agents are characterized by a high degree of cytotoxicity [6]. Fibrin is a versatile, FDA-approved material that is known to form hydrogels with tunable mechanical properties. However, fibrin itself does not mimic the complexity of the extracellular microenvironment of the heart. The objectives of this work were to develop hybrid cardiac ECM-fibrin hydrogels and to determine the effects of mild crosslinking agents on the structural and mechanical properties of the hybrid scaffolds, as well as the effects on cell viability and function.