Optimized Bioactive PCL–PEO/ <i>Piper betle</i> L. Nanoscaffolds: Next-Generation Biomaterial for Accelerated Wound Healing and Tissue Regeneration

Polycaprolactone (PCL), despite its extensive use in biomedical engineering, is limited by its slow degradation and hydrophobic nature. To address these shortcomings and enhance its biological functionality, it is blended with poly(ethylene oxide) (PEO) and loaded with natural bioactive compounds, enhancing its hydrophilicity, electrospinnability, biodegradability, bioresponsiveness, and multifunctionality. Therefore, this study aimed to fabricate PCL/PEO optimized blended nanoscaffolds (BNS) incorporating betel leaf extracted particles (betel leaf extracts (BLE)) for the first time through electrospinning for applications in advanced tissue engineering and wound healing. BLE particles (725.08 ± 224.22 nm) were obtained from Piper betle L. through maceration and sonication-assisted ethanolic extraction, followed by drying. Optimized PCL/PEO (10:1 w/w) blended solutions along with 10–30% (w/w relative to polymer) bioactive BLE were used to fabricate the desired scaffolds, and their physicochemical and mechanical properties were evaluated by scanning electron microscopy, fourier transform infrared, X-ray diffraction, thermogravimetric analysis, contact angle, swelling ratio, and tensile tests. In addition, antibacterial susceptibility, antioxidant activity, biodegradation, cell viability (A549 line), and in vitro wound closure assays were performed to assess the biological performance. The results demonstrated enhanced surface wettability with the fiber diameter increasing by 20.3–27.57% upon swelling. BLE-BNS exhibited 28–46.13% antioxidant activity, strong antibacterial effects, and acceptable biocompatibility. Notably, wound healing assays demonstrated 1.96–3.14-fold faster closure than the controls. These findings demonstrate that a BLE-loaded BNS is a multifunctional and fascinating choice for advanced wound healing and tissue engineering.