Cardiac Bio-Nanonetwork: Extracellular Matrix Modeling for the Propagation of Extracellular Vesicles

Novel non-invasive procedures, such as targeted drug delivery may enhance the efficacy of treatments of cardiac disorders. A possible solution is to utilize a molecular communication paradigm based on cell-derived nano-sized vesicles --- extracellular vesicles (EVs) --- that can be used as vehicles for therapeutic biological cargo. EVs can be engineered with specific cell-targeting transmembrane proteins to improve their pharmacokinetic properties. Here, we study the transport of EVs in a non-cellular component of cardiac tissue referred to as the cardiac extracellular matrix (ECM). We inspect EV diffusion and advection in cardiac ECM by considering 1) tortuosity, which describes the convoluted pathway of EV transportation, 2) volume fraction, which characterizes the porosity of the cardiac ECM; and 3) EV degradation according to their half-life in the body. We analytically describe the EV transportation dynamics via a partial differential equation and solve it numerically using finite element methods. The presented findings indicate that EV propagation is dependent on the cardiac ECM hindrance sources. Bulk flow in the cardiac ECM, however, can mediate the EVs to reach their distant target cells.