Biomimetic Gradient Microporous Scaffold with a Triply Periodic Minimal Surface Enhances Osseointegration by Modulating Macrophage Polarization

Bionically designed gradient microporous scaffolds have garnered considerable attention in orthopedics and bone tissue engineering for their ability to replicate the gradual pore transition from cortical to trabecular bone, thereby integrating mechanical strength with biological functionality essential for bone regeneration. However, the immune-inflammatory response induced by biomaterial implantation can impair osseointegration, potentially leading to chronic inflammation or implant failure. To address this limitation, the present study utilized selective laser melting to fabricate a biomimetic gradient microporous titanium alloy scaffold based on a triply periodic minimal surface architecture (pore size: 650 to 350 μm), with solid nonporous scaffolds (0 μm) and uniform microporous scaffolds (500 μm) serving as controls. The study comprehensively evaluated the role of the gradient scaffold in both osseointegration and immune modulation. Mechanical testing confirmed that the gradient scaffold possessed an elastic modulus well matched to that of bone tissue, thereby mitigating stress shielding. In vitro assays revealed that, relative to the control scaffolds, the gradient scaffold more effectively promoted macrophage polarization toward the M2 phenotype while enhancing the osteogenic differentiation capacity of bone marrow mesenchymal stem cells. Subsequent in vivo experiments demonstrated that the gradient microporous titanium alloy scaffold attenuated local inflammatory responses and facilitated new bone formation. Collectively, these findings provide compelling evidence for the dual role of titanium alloy gradient biomimetic microporous structures in immune regulation and osseointegration, offering critical insights for the optimization of scaffold designs in bone tissue regeneration.