Additively Manufactured Biodegradable Zn‐Based Porous Scaffolds to Suppress Osteosarcoma and Promote Osteogenesis

Abstract Postoperative therapies for osteosarcoma present substantial challenges due to tumor recurrence and extensive bone defects. To tackle these challenges, laser powder bed fusion is utilized to fabricate biodegradable Zn‐Li porous scaffolds that supress tumors and promote osteogenesis. After the structure design and composition selection, the Zn‐0.8Li porous scaffold with Gyroid unit optimally balances the co‐release of Zn²⁺ and Li⁺ during degradation, resulting in favorable antitumor and osteogenic effects. In vitro, the Zn‐0.8Li scaffold significantly inhibits osteosarcoma progression by suppressing tumor cell proliferation, promoting apoptosis, alleviating migration, and simultaneously promotes osteogenic differentiation through the enhanced expression of osteogenic markers. In vivo, the Zn‐0.8Li scaffold inhibits the malignant osteosarcoma behavior and facilitates bone regeneration in areas with bone defects. Transcriptomic analysis further reveals that the simultaneous release of Zn²⁺ and Li⁺ from the biodegradable Zn‐0.8Li scaffold contributes to anti‐osteosarcoma activity by downregulating PI3K/Akt signaling pathways. Taken together, the Zn‐0.8Li porous scaffold fabricated using laser powder bed fusion with enhanced antitumor and osteogenic properties is a promising alternative for the postoperative management of osteosarcoma.