Cryogenic 3D-printed PLGA/nano-selenium scaffold for bone regeneration: a dual-functional strategy synergistically regulating macrophage polarization and osteogenic differentiation

Abstract

Background: Autologous and allogeneic bone grafts are primarily used for bone tissue defects; however, they have limitations such as limited supply, donor site morbidity, and immune rejection risks. Therefore, substitute synthetic bone grafts are required. This study aims to develop a cryogenic 3D-printed PLGA/HA@SeNPs scaffold that synergistically regulates macrophage polarization and osteogenic differentiation for bone regeneration. Methods: Using low-temperature 3D printing combined with freeze-drying technology, a hierarchically porous PLGA/HA@SeNPs composite scaffold was fabricated by compositing poly(lactic-co-glycolic acid) (PLGA) with hyaluronic acid-modified selenium (Se) nanoparticles (HA@SeNPs), enabling sustained immunomodulation and osteogenic activity through its engineered microtopography and bioactive components. Results: In vitro evaluations confirmed that the unique microstructure and sustained Se release from HA@SeNPs synergistically promoted macrophage polarization toward the M2 phenotype, accompanied by enhanced osteogenic differentiation as shown by upregulation of Runx2 and osteocalcin and accelerated matrix mineralization. Implantation into a rat femoral critical-sized defect model resulted in substantially improved bone repair and architectural restoration. Conclusions: These findings indicate that the intrinsic physicochemical properties of the PLGA/HA@SeNPs scaffold orchestrate a favorable osteo-immune environment, positioning it as a promising platform for bone regeneration.

Keywords

Cryogenic 3D printing / Nano-selenium / Immunomodulation / Bone regeneration / Macrophage polarization / Osteogenesis

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