3D-printed PLA/β-TCP scaffold functionalized with PDA and neobavaisoflavone-loaded PEG hydrogel for enhanced bone repair.

Bone defects remain a formidable clinical challenge, motivating the development of multifunctional scaffolds that better recapitulate the bone microenvironment. Here, we designed a 3D-printed polylactic acid/β-tricalcium phosphate (PLA/β-TCP, PT) scaffold functionalized with a polydopamine (PDA) layer and a polyethylene glycol (PEG) hydrogel for sustained delivery of the bioactive flavonoid neobavaisoflavone (NB). The resulting PT/PDA/PEG/NB scaffold promoted bone marrow mesenchymal stem cell (BMSC) proliferation, migration, and osteogenic differentiation, while reducing pro-inflammatory cytokine expression and oxidative stress and enhancing M2 macrophage polarization in vitro. Mechanistically, sustained NB release activated the Nrf2 antioxidant signaling pathway, linking redox regulation with immune modulation. In vivo evaluation using a rat skull defect model demonstrated that the PT/PDA/PEG/NB scaffolds significantly enhanced bone repair compared with control scaffolds. Collectively, this multifunctional scaffold integrates immunomodulation, antioxidative defense, and osteoinduction, offering a promising platform for effective bone defect repair and advanced orthopedic implant design.