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Repair of osteoporotic bone defects (OBD) remains a clinical challenge due to dysregulated bone homeostasis, characterized by impaired osteogenesis and excessive osteoclast activity. While drug-loaded 3D-printed scaffolds hold great potential in the restoration of bone homeostasis for enhanced OBD repair, achieving the controlled release and targeted delivery of drugs in a 3D-printed scaffold is still unmet. Herein, we developed an electrostatic encapsulation strategy to motivate 3D-printed polyelectrolyte scaffolds (APS@P) with bone-targeting liposome formulation of salvianolic acid B (SAB-BTL). Benefiting from this strategy, SAB, an unstable and untargetable plant-derived osteogenic compound, was effectively encapsulated in APS@P, demonstrating stable and precise delivery with improved therapeutic efficacy. Owing to SAB-mediated bone homeostasis, APS@P significantly promoted angiogenesis and new bone formation while suppressing bone resorption, resulting in a significant 146 % increase in bone mass and improved microstructure compared to the OBD group. It was confirmed that the encapsulation of SAB into APS@P could promote the osteogenic differentiation of MSCs by stimulating Tph2/Wnt/β-catenin signaling axis, coupled with the stimulation of type H angiogenesis and the suppression of RANKL-mediate bone resorption, thereby enhance OBD repair. This study provides a universal platform for enhancing the bioactivity of tissue-engineered scaffolds, offering an effective solution for the efficient regeneration of osteoporotic bone. TOC: An electrostatic encapsulation strategy is presented to motivate 3D-printed polyelectrolyte scaffolds with a stable and precise delivery of bone-targeting liposome formulation of salvianolic acid B. It demonstrates a significant promotion of new bone formation for efficient repair of osteoporotic bone defects by regulating the Tph2/Wnt/β-catenin pathway for osteogenesis, enhancing type H angiogenesis, and suppressing bone resorption. • Developing an electrostatic encapsulation strategy to fabricate a bioactive 3D-printed polyelectrolyte scaffold. • Realizing the 3D-printed scaffold with a stable and precise delivery of a nano bone-targeting SAB-loaded liposome. • Demonstrating an improved therapeutic efficacy of APS@P for efficient repair of osteoporotic bone defects.
Gao et al. (2024) studied this question.