Electrospinning is one of the most effective approaches to fabricate tissue-engineered scaffolds composed of nano-to sub-microscale fibers that simulate a native extracellular matrix. However, one major concern about electrospun scaffolds for tissue repair and regeneration is that their small pores defined by densely compacted fibers markedly hinder cell infiltration and tissue ingrowth. To address this problem, researchers have developed and investigated various methods of manipulating scaffold structures to increase pore size or loosen the scaffold. These methods involve the use of physical treatments, such as salt leaching, gas foaming and custom-made collectors, and combined techniques to obtain electrospun scaffolds with loose fibrous structures and large pores. This article provides a summary of these motivating electrospinning techniques to enhance cell infiltration of electrospun scaffolds, which may inspire new electrospinning techniques and their new biomedical applications.
Tissue engineering techniques using novel scaffolding materials offer potential alternatives for managing tendon disorders. An ideal tendon tissue engineered scaffold should mimic the three-dimensional (3D) structure of the natural extracellular matrix (ECM) of the native tendon. Here, we propose a novel electrospun nanoyarn network that is morphologically and structurally similar to the ECM of native tendon tissues. The nanoyarn, random nanofiber, and aligned nanofiber scaffolds of a synthetic biodegradable polymer, poly(L-lactide-co-ε-caprolactone) [P(LLA-CL)], and natural collagen I complex were fabricated using electrospinning. These scaffolds were characterized in terms of fiber morphology, pore size, porosity, and chemical and mechanical properties for the purpose of culturing tendon cells (TCs) for tendon tissue engineering. The results indicated a fiber diameter of 632 ± 81 nm for the random nanofiber scaffold, 643 ± 97 nm for the aligned nanofiber scaffold, and 641 ± 68 nm for the nanoyarn scaffold. The yarn in the nanoyarn scaffold was twisted by many nanofibers similar to the structure and inherent nanoscale organization of tendons, indicating an increase in the diameter of 9.51 ± 3.62 μm. The nanoyarn scaffold also contained 3D aligned microstructures with large interconnected pores and high porosity. Fourier transform infrared analyses revealed the presence of collagen in the three scaffolds. The mechanical properties of the sample scaffolds indicated that the scaffolds had desirable mechanical properties for tissue regeneration. Further, the results revealed that TC proliferation and infiltration, and the expression of tendon-related ECM genes, were significantly enhanced on the nanoyarn scaffold compared with that on the random nanofiber and aligned nanofiber scaffolds. This study demonstrates that electrospun P(LLA-CL)/collagen nanoyarn is a novel, 3D, macroporous, aligned scaffold that has potential application in tendon tissue engineering.