Sustainable fabrication of heparin-conjugated poly(ε-caprolactone)/gelatin fibers for tendon tissue engineering

Tendon injuries present significant healing challenges due to poor vascularization and limited regenerative capacity, requiring engineered scaffolds that provide both mechanical support and biological guidance. Current electrospinning methods for fabricating such fibrous scaffolds commonly rely on toxic solvents, creating environmental and safety concerns. Here we report the fabrication of electrospun aligned polycaprolactone/gelatin (PCL/GEL) fibers with covalently conjugated heparin (HEP) using a benign binary solvent system. Uncrosslinked PCL/GEL fibers had an average size of 1.0 ± 0.5 μm and a highly aligned fiber orientation, with chemical crosslinking and HEP conjugation reducing both fiber size and directionality due to the formation of interconnected networks. The crosslinking process improved fiber stability in aqueous medium, allowing for >78% initial weight to be retained after 14 days. HEP conjugation yielded 15.3 ± 1.5 μg/mL per mg of fibers, with >91% HEP still covalently bound to PCL/GEL fibers after 14 days of incubation. PCL/GEL fibers significantly upregulated gene expression of tenogenic markers in amniotic epithelial cells (AECs) seeded on them for 48 h, while HEP-conjugated fibers proved to possess an anti-inflammatory immunomodulatory activity on AECs.