Modulating Surface Properties and Osteoblast Responses in Bone Regeneration via Positive and Negative Charges during Electrospinning of Poly( <scp>l</scp> -lactide- <i>co</i> -ε-caprolactone) (PLCL) Scaffolds

The global demand for faster and more effective bone regeneration calls for biomimetic scaffolds that actively guide cell behavior beyond providing structural support. Electrospinning offers unique opportunities to tailor scaffold properties, yet the influence of positive and negative voltage polarities during fabrication on cell-material interactions remains largely unexplored. Here, we investigate poly(l-lactide-<i>co</i>-ε-caprolactone) (PLCL) scaffolds, a statistical copolymer combining strength and elasticity, produced under positive (PLCL+) and negative (PLCL-) polarity. Both scaffold types display comparable morphologies and bulk chemistry. However, X-ray photoelectron spectroscopy reveals charge dependent surface chemistry, with PLCL- enriched in O═C and O-C groups. Zeta potential results highlight pronounced voltage polarity effects under aqueous conditions at pH 7.5, showing -29.19 mV for PLCL+ and -34.77 mV for PLCL-. Biologically, both scaffolds support rapid osteoblast attachment, with robust filopodia and collagen type I deposition by day 14. Strikingly, PLCL+ scaffolds promote deeper cellular infiltration and broader cytoskeletal distribution, whereas PLCL- scaffolds enhance proliferation, but with a flatter cell morphology. These findings reveal that subtle, charge-driven surface chemical differences in random copolymer scaffolds profoundly modulate osteoblast behavior. This work identifies electrospinning voltage polarity as a powerful yet underutilized design parameter for engineering next-generation scaffolds for bone tissue regeneration.