Fibrous microstructure has drawn extensive attention in tissue engineering due to its common presence in connective and muscle tissues. This paper reviews the latest advances in electrospinning as a nanofiber fabrication technique for biomimetic scaffolds. Specifically, we focus on scaffolds with gradients in element and structure, 3 D nanofiber scaffolds, and hydrogel scaffolds incorporated with nanofibers. Future directions of electrospinning research for tissue engineering are to realize the full potential of integrating the tunable 3 D fibrous microarchitecture in scaffold manufacturing at a clinically relevant scale, and to develop novel micro- and nano-scaffold architecture with modulated functionality for optimal tissue regeneration.

The creation of biomimetic cell environments with micro and nanoscale topographical features resembling native tissues is critical for tissue engineering. To address this challenge, this study focuses on an innovative electrospinning strategy that adopts a symmetrically divergent electric field to induce rapid self-assembly of aligned polycaprolactone (PCL) nanofibers into a centimeter-scale architecture between separately grounded bevels. The 3D microstructures of the nanofiber scaffolds were characterized through a series of sectioning in both vertical and horizontal directions. PCL/collagen (type I) nanofiber scaffolds with different density gradients were incorporated in sodium alginate hydrogels and subjected to elemental analysis. Human fibroblasts were seeded onto the scaffolds and cultured for 7 days. Our studies showed that the inclination angle of the collector had significant effects on nanofiber attributes, including the mean diameter, density gradient, and alignment gradient. The fiber density and alignment at the peripheral area of the 45°-collector decreased by 21% and 55%, respectively, along the z-axis, while those of the 60°-collector decreased by 71% and 60%, respectively. By altering the geometry of the conductive areas on the collecting bevels, polyhedral and cylindrical scaffolds composed of aligned fibers were directly fabricated. By using a four-bevel collector, the nanofibers formed a matrix of microgrids with a density of 11%. The gradient of nitrogen-to-carbon ratio in the scaffold-incorporated hydrogel was consistent with the nanofiber density gradient. The scaffolds provided biophysical stimuli to facilitate cell adhesion, proliferation, and morphogenesis in 3D.