Synergetic effect of electrospun PCL fiber size, orientation and plasma-modified surface chemistry on stem cell behavior

Electrospun polymeric meshes have revolutionized the evolving tissue engineering field for their extracellular matrix mimicry. However, besides the fibrous architecture, cell-material interactions are also critically and synergistically influenced by specific surface chemical and topographical features, such as fiber size and fiber orientation. To examine these effects in detail, random polycaprolactone (PCL) fibers with average diameters of 232, 500 and 1272 nm and highly aligned fibers with diameters of 225, 482 and 1173 nm are electrospun in this work. Surface biofunctionalization is then achieved by plasma-treating the fibers using argon at medium pressure. Results reveal a significantly enhanced wettability on plasma-treated fibers due to the incorporation of oxygen-containing functionalities on their surface. A treatment time of 15 s is shown to preserve the scale and morphology of all fiber conditions. However, an extended plasma exposure starts damaging the fibers with a growing risk of drastic alterations on thicker and random fibers compared to thinner and aligned fibers. These diverse responses stem from the distinct molecular chain arrangement and crystallinity of different fiber sizes and orientations. The fibers bioresponsive properties are also profoundly investigated in this study by seeding and evaluating adipose-derived stem cells (ADSCs) performance. Plasma treatment strikingly enhances the cell metabolic activity, adhesion, proliferation and cytoplasmic remodeling on all samples. Cells adhere multi-directionally on random fibers with a gradual change from dilated and more circular to a stretched out and more elongated shape on increasing diameters. In contrast, ADSCs overextend in a bipolar and aligned fashion on aligned fibers with a tendency to attach on fewer fibers with increasing fiber diameter. A critical distinction is the cell infiltration in-between the pores of the thickest fibers. Overall, plasma-treated fibers are very promising substrates for multiple tissue engineering applications. Since the desired ADSCs behavior observed on distinct fiber size and orientation strongly depends on a specific end-application, this work constitutes a picture-perfect reference paving the way towards the optimization of the previous generation of scaffolds.