Fabrication and in Vivo Evaluation of Hybrid Squalene-Loaded Nanofiber Scaffolds Based on Poly(ε-Caprolactone)/Polyvinyl Alcohol/Chitosan for Wound Healing Applications

Abstract

Chronic wounds significantly burden global healthcare systems, necessitating innovative solutions. Hybrid electrospun nanofibers are promising for enhancing wound healing and controlled drug delivery. This study focused on developing and characterizing hybrid nanofibrous scaffolds made from polycaprolactone (PCL), polyvinyl alcohol (PVA), and chitosan (Cs), infused with squalene (SQ) to improve healing in a rat model of full-thickness wounds. The scaffolds were created using coaxial electrospinning, with PCL as the shell and a PVA/Cs mixture as the SQ-loaded core. Characterization involved Fourier-transform infrared spectroscopy (FTIR), Scanning Electron Microscope (SEM), mechanical properties, contact angle measurements, swelling, degradation, drug release, cell attachments and cytotoxicity assays. After implantation in a rat model for 14 days, histopathological assessments evaluated inflammation, re-epithelialization, and collagen deposition. The hybrid nanofibers maintained consistent morphology with smooth surfaces and no bead formation. Diameters were 219 ± 33.4 nm for the neat scaffold and 227 ± 59.7 nm, 167.3 ± 35.9 nm, and 126.7 ± 39.75 nm for SQ2%, SQ3%, and SQ4%, respectively. SQ-loaded scaffolds exhibited reduced swelling ratio, hydrophilicity, and degradation rate, alongside improved tensile strength (194% increase in SQ4% vs. control), sustained SQ release (40% over 14 days for SQ3%), as well as considerable reducing in wound sizes (90% reduction in SQ2%). The PCL-PVA/Cs/SQ2% formulation notably reduced inflammation while promoting re-epithelialization and collagen deposition. The PCL-PVA/Cs/SQ nanofiber scaffolds demonstrated superior properties that effectively modulated inflammation and promoted wound healing. They represent a promising strategy for enhancing wound repair.

Graphical Abstract