Strontium oxide-functionalized 3D-printed polycaprolactone/β-tricalcium phosphate nanocomposite scaffolds with osteogenic microenvironment remodeling for accelerated bone regeneration

The repair of critical bone defects resulting from trauma, infection, tumors, and congenital malformations poses significant clinical challenges. The combination of medical-grade polycaprolactone (PCL) and β-tricalcium phosphate (β-TCP) is widely investigated for developing synthetic bone graft substitutes, attracting considerable interest in regenerative medicine. However, the material's inherent lack of osteogenic capacity remains a bottleneck to its widespread clinical application. This study synthesized a strontium oxide (SrO)-functionalized three-dimensional (3D)-printed polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) composite scaffold. Gradient SrO-doped (0-2.0 wt %) 3D printed scaffolds (3D PTSr) were fabricated by melt blending and direct ink writing (DIW) technology, and their physicochemical and biological properties were systematically characterized. Scanning electron microscopy (SEM) showed that the 3D PTSr scaffold had a precisely regulated macroscopic pore structure (pore size ∼ 1 mm) and uniformly distributed Sr element. When the doping amount of SrO was 1.5 wt %, the scaffold exhibited the best comprehensive performance: the surface contact angle was reduced to 64.78° ± 0.54°, and the weight loss rate was 42.83 ± 0.02 % after 4 weeks of in vitro degradation. At the same time, it showed the sustained release characteristics of Sr²⁺ for 56 days (cumulative release of 10.42 ppm). Mechanical tests showed that the compressive strength (5.64 ± 0.04 MPa) and tensile strength (2.75 ± 0.16 MPa) were significantly better than the control group (p < 0.05). In vitro biomimetic mineralization experiments confirmed that SrO functionalization facilitated dense calcium-phosphate composite layer formation. In vitro experiments demonstrated that the 3D PTSr1.5 scaffold significantly promoted the proliferation of MC3T3-E1 cells, and its osteogenic differentiation ability was verified by increasing alkaline phosphatase (ALP) activity and calcium nodule formation. Implantation of 3D PTSr1.5 scaffold into rat cranial defects significantly enhanced bone regeneration at 12 weeks versus controls. Histological analysis confirmed substantial regeneration of mature bone tissue and collagen fibers within the defect area. This study reveals the molecular mechanism of SrO functionalization promoting bone regeneration by regulating the synergistic effect of material degradation-ion release-topology, and provides a theoretical basis and technical reserve for the development of next-generation intelligent bone repair materials.