Bioinspired PCL-based composite scaffolds produced via hot melt extrusion and fused filament fabrication: An integrated workflow for enhanced bone regeneration

This study presents a comprehensive and integrated workflow for fabricating bioinspired, macroporous 3D scaffolds tailored for bone tissue engineering. Poly-(epsilon-caprolactone) (PCL) served as the base polymer, enriched with nature-derived fillers such as sodium alginate and microcrystalline cellulose, along with bioactive nanohydroxyapatite ceramics, to enhance hydrophilicity, bioactivity, and cellular interactions. A combined manufacturing approach was implemented to ensure uniform filler distribution and optimized scaffold performance: hybrid pellets preparation and composite filament production through Hot Melt Extrusion (HME), followed by scaffold fabrication using Fused Filament Fabrication (FFF). This multistep process allowed precise control over material composition, ensuring compatibility and consistency across fabrication stages. The 3D printed scaffolds were characterized for printability, architecture, surface topography, thermal and mechanical properties, degradation behavior, swelling capacity, and drug release profiles. Incorporating nature- derived fillers improved hydrophilicity, swelling behavior, and biodegradation kinetics, while nanohydroxyapatite enhanced mechanical strength and sustained release of dexamethasone. In vitro tests using murine pre-osteoblasts confirmed scaffold biocompatibility and osteogenic potential, promoting cell proliferation and differentiation. The findings underscore the potential of this integrated workflow for advancing scaffold design and bone regeneration.