Biomimetic three-dimensional scaffolds with aligned electrospun nanofibers and enlarged pores for enhanced cardiac cell colonization

• Biomimetic 3D scaffolds with aligned nanofibers and enlarged interconnected pores are fabricated. • Thanks to a self-organization mechanism, a scaffold made of isolated islands of microparticles embedded in a network of loosely packed and highly aligned nanofibers is obtained. • The scaffolds having an open porosity with enlarged interconnected pores allows the efficient 3D colonization of cardiac cells through a network of aligned nanofibers. • Longitudinal and transversal tensile measurements highlighted the anisotropy of the scaffolds with a mechanical behavior mimicking that of cardiac tissue. Among the wide range of biomimetic scaffolds, those made of aligned nanofibers represent an important class for tissue engineering applications, and particularly for cardiac repair. Electrospinning is a powerful technique allowing the fabrication of scaffolds with aligned nanofibers. However, the resulting morphology is characterized by low porosity and small pore size due to the formation of a compact structure of aligned fibers preventing cell colonization inside the scaffold. In the present work, supported by numerical simulation, it is demonstrated that when optimal electrostatic interactions occur during the simultaneous deposition of electrospun nanofibers and electrosprayed microparticles on a collector rotating at high speed, a 3D structured scaffold is obtained. Thanks to a self-organization mechanism, islands of microparticles intercalate inside a network of loosely packed and highly aligned nanofibers. In the case of poly(lactic acid) electrospinning and poly(glycerol sebacate)/cyclodextrin electrospraying, the resulting 3D biomimetic scaffold, deeply investigated by X-ray microtomography and mechanical characterization, shows an open porosity with enlarged interconnected pores with a mechanical behavior mimicking that of cardiac tissue. Finally, after functionalizing the fiber surface using laminin, it is shown an efficient 3D colonization of cardiac cells through a network of aligned nanofibers.