Evaluation of the Biological Response to Coating 3D-Printed PLA Scaffolds with Coaxial Gelatin-Based Electrospun Fibers

Bone grafting remains limited, and the strategies to design even more structurally complex scaffolds-able to reproduce the hierarchical architecture of bone extracellular matrix-are rapidly growing. In this study, we report the fabrication of a hierarchically structured scaffold produced by layering poly(ε-caprolactone)/gelatin (PCL/Gt) or poly(lactic acid)/gelatin (PLA/Gt) electrospun nanofibers via coaxial electrospinning onto 3D-printed poly(lactic acid) (PLA) scaffolds via fused deposition modeling (FDM). After the printing process, PLA disks (10 × 1 mm, 20% infill, ~80% porosity, pore size ~1.57 mm) were coated with core/shell (PCL/Gt, PLA/Gt) fibers to investigate the in vitro interfacial response of osteoblasts in comparison with monocomponent fibrous coatings (PCL, PLA, Gt). SEM and TEM confirmed that core/shell fibers exhibited bead-free morphologies, with a significant reduction in fiber diameter (≈287-316 nm) and higher interfibrillar porosity compared to monocomponent fibers. FTIR and thermogravimetric analyses indicated the presence of hydrogen bonding between the polyester and gelatin, and the absence of residual solvent after deposition. At the same time, water contact angle measurements confirmed an increase in hydrophilic properties from 80-86° to 120° ascribable to the presence of gelatin. Accordingly, in vitro response of human fetal osteoblasts (hFOB 1.19) exhibited an evident improvement in the case of Gt-based fibrous coatings (i.e., PCL/Gt and PLA/Gt) in terms of early adhesion (4-24 h) and metabolic activity from 3 to 21 days, cell spreading into star-shaped morphologies, formation of extracellular matrix, and mineral phase deposition. In more detail, a remarkable increase in alkaline phosphatase activity was observed in Gt-based coaxial coatings from day 7 onward, with the highest values recorded for PLA/Gt. Overall, we demonstrated that the Gt-based coaxial fibrous coating provided a mix of topological and biochemical cues that synergistically promoted key osteoblast activities at the interface, supporting the regeneration of new bone tissue in highly tailored 3D-printed scaffolds, thus suggesting a promising strategy for personalized regenerative medicine.