Thickness-controllable electrospun fibers promote tubular structure formation by endothelial progenitor cells

Abstract

Jong Kyu Hong,1,2 Ju Yup Bang,3 Guan Xu,4 Jun-Hee Lee,1 Yeon-Ju Kim,1 Ho-Jun Lee,5 Han Seong Kim,3 Sang-Mo Kwon1,2,6 1Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan, South Korea; 2Conversence Stem Cell Research Center, Medical Research Institute, School of Medicine, Pusan National University, Yangsan, South Korea; 3Department of Organic Material Science, Pusan National University, Geumjeong-gu, Busan, South Korea; 4Department of Radiology, School of Medicine, University of Michigan, Ann Arbor, MI, USA; 5Department of Electrical Engineering, Pusan National University, Geumjeong-gu, Busan, South Korea; 6Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Department of Physiology, Pusan National University School of Medicine, Yangsan, South Korea Abstract: Controlling the thickness of an electrospun nanofibrous scaffold by altering its pore size has been shown to regulate cell behaviors such as cell infiltration into a three-dimensional (3D) scaffold. This is of great importance when manufacturing tissue-engineering scaffolds using an electrospinning process. In this study, we report the development of a novel process whereby additional aluminum foil layers were applied to the accumulated electrospun fibers of an existing aluminum foil collector, effectively reducing the incidence of charge buildup. Using this process, we fabricated an electrospun scaffold with a large pore (pore size >40 µm) while simultaneously controlling the thickness. We demonstrate that the large pore size triggered rapid infiltration (160 µm in 4 hours of cell culture) of individual endothelial progenitor cells (EPCs) and rapid cell colonization after seeding EPC spheroids. We confirmed that the 3D, but not two-dimensional, scaffold structures regulated tubular structure formation by the EPCs. Thus, incorporation of stem cells into a highly porous 3D scaffold with tunable thickness has implications for the regeneration of vascularized thick tissues and cardiac patch development. Keywords: electrospinning, nanofibrous scaffold, tunable thickness, vascularization, stem cell