Study of bioactive 3D-printed scaffolds incorporating zinc-based MOF for bone defect repair and anti-inflammatory applications

Abstract

The development of bioactive scaffolds capable of orchestrating osteogenesis while modulating inflammatory responses remains a critical challenge in bone tissue engineering. To address this unmet need, we engineered a multifunctional composite scaffold through precise integration of poly(lactic-co-glycolic acid) (PLGA), type I collagen, zinc-imbued metal-organic frameworks (Zn-MOFs), and macrophage chemotactic factor (MCF) via extrusion-based 3D printing. Systematic biological assessments in vitro revealed the scaffold's remarkable osteoinductive capacity, evidenced by significant upregulation of alkaline phosphatase (ALP) activity (2.78 ± 0.10 fold increase vs control, p < 0.05) and enhanced collagen type I deposition (10.79 ± 1.12 fold increase vs control, p < 0.05) within 14 days of culture. In vivo implantation in rat femoral defect models demonstrated superior bone regeneration outcomes, with micro-CT analysis showing bone volume/total volume (BV/TV) 31.39 ± 3.04 % compared to 16.44 ± 3.26 % in control (P < 0.05). The Zn-MOF component mediated sustained release of Zn2+ ions (cumulative release: 89.6 ± 9.08 % over 18 days). This dual-functional system synergistically combines MCF-driven cellular recruitment with Zn2+-mediated immunomodulation, creating a pro-regenerative microenvironment. Our findings not only demonstrate the feasibility of 3D-printed multi-material constructs for complex tissue engineering applications but also establish a new paradigm for developing smart biomaterials that concurrently address biological regeneration and inflammatory control.

Keywords

• Zn-MOF
• Macrophage chemotactic factors (MCF)
• 3D printed scaffold
• Bone regeneration