Comparative evaluation of melt- <i>vs.</i> solution-printed poly(ε-caprolactone)/hydroxyapatite scaffolds for bone tissue engineering applications

Material extrusion-based three-dimensional (3D) printing is a widely used manufacturing technology for fabricating scaffolds and devices in bone tissue engineering (BTE). This technique involves two fundamentally different extrusion approaches: solution-based and melt-based printing. In solution-based printing, a polymer solution is extruded and solidifies <i>via</i> solvent evaporation, whereas in melt-based printing, the polymer is melted at elevated temperatures and solidifies as it cools post-extrusion. Solution-based printing can also be enhanced to generate micro/nano-scale porosity through phase separation by printing the solution into a nonsolvent bath. The choice of the printing method directly affects scaffold properties and the biological response of stem cells. In this study, we selected polycaprolactone (PCL), a biodegradable polymer frequently used in BTE, blended with hydroxyapatite (HA) nanoparticles, a bioceramic known for promoting bone formation, to investigate the effects of the printing approach on scaffold properties and performance <i>in vitro</i> using human mesenchymal stem cells (hMSCs). Our results showed that while both printing methods produced scaffolds with similar strut and overall scaffold dimensions, solvent-based printing resulted in porous struts, higher surface roughness, lower stiffness, and increased crystallinity compared to melt-based printing. Although stem cell viability and proliferation were not significantly influenced by the printing approach, melt-printed scaffolds promoted a more spread morphology and exhibited pronounced vinculin staining. Furthermore, composite scaffolds outperformed their neat counterparts, with melt-printed composite scaffolds significantly enhancing bone formation. This study highlights the critical role of the printing process in determining scaffold properties and performance, providing valuable insights for optimizing scaffold design in BTE.