Microstructure-tailored β-tricalcium phosphate scaffolds utilize degradation-guided osteoclast suppression to accelerate bone regeneration

Abstract

β-Tricalcium phosphate (β-TCP) has been a valuable artificial bone material in clinical applications owing to its bioactivity, osteoconductivity, and degradability. However, the inappropriate degradation rate of β-TCP implants is one of the most important factors affecting the bone regeneration process, and it remains a challenge to effectively regulate β-TCP degradation for adapting to bone regeneration. To address this, we fabricated β-TCP scaffolds with strut sizes ranging from 300 to 900 µm by using digital light processing (DLP) printing. The results in vitro showed that a strut size-dependent degradation gradient, and the scaffolds with a 300 µm strut size had the fastest degradation rate. Furthermore, these scaffolds with smaller strut sizes (particularly 300 µm) enhanced the adhesion and proliferation of mBMSCs, increased alkaline phosphatase activity, and promoted the osteogenic-related gene expression. Notably, these scaffolds with smaller strut sizes, especially 300 µm, inhibited osteoclast differentiation due to the suppressive effect of Ca²⁺ and PO₄³⁻ from β-TCP degradation on osteoclastogenesis. Finally, the scaffold with a 300 µm strut size significantly inhibited the formation of multinucleated osteoclasts, accelerating bone regeneration and promoting the maturation of new bone during a 24-week tibial defect repair. This work suggests that microstructure-driven degradation tuning of β-TCP scaffolds can optimize bone repair by synchronizing material resorption with osteogenesis and inhibiting osteoclast differentiation.