A 3D-printed PCL/Ta/Sr-HA composite scaffold enhances osteogenesis and modulates macrophage phenotypic responses.

Complex bone defects present a persistent clinical challenge. Three-dimensional (3D) printing offers a feasible approach for fabricating scaffolds with tailored architectures. In this study, we engineered a series of 3D-printed composite scaffolds by sequentially incorporating tantalum nanoparticles (Ta) and strontium-doped hydroxyapatite (Sr-HA) into a polycaprolactone (PCL) matrix, creating four experimental groups: PCL, PCL/Ta, PCL/Ta/HA, and PCL/Ta/Sr-HA. The scaffolds were evaluated for physicochemical properties, rBMSC osteogenic responses, and macrophage marker expression. The PCL/Ta/Sr-HA composite improved rBMSC adhesion and osteogenic differentiation compared with PCL, PCL/Ta, and PCL/Ta/HA scaffolds. In macrophage-response assays, the PCL/Ta scaffold was associated with a more pro-inflammatory macrophage profile, whereas Sr-HA incorporation shifted the response toward an anti-inflammatory M2-like phenotype. In a rat cranial defect model, the PCL/Ta/Sr-HA scaffold was associated with greater bone regeneration at 4 weeks. A murine subcutaneous implantation model also indicated increased M2 macrophage presence around the PCL/Ta/Sr-HA implants. These effects may be related to the improved surface wettability, increased nanoscale roughness, and sustained Sr2⁺ release of the PCL/Ta/Sr-HA scaffold. These findings suggest that Sr-HA incorporation may improve the osteogenic performance of PCL/Ta scaffolds while shifting early macrophage responses toward a CD206-positive, M2-like profile.