Sono-activable and biocatalytic 3D-printed scaffolds for intelligently sequential therapies in osteosarcoma eradication and defect regeneration

Xiao Rong, Sutong Xiao, Wei Geng, Bihui Zhu, Ping Mou, Zichuan Ding, Boqing Zhang (), Yujiang Fan, Li Qiu () and Chong Cheng ()
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Xiao Rong: Sichuan University
Sutong Xiao: Sichuan University
Wei Geng: Sichuan University
Bihui Zhu: Sichuan University
Ping Mou: Sichuan University
Zichuan Ding: Sichuan University
Boqing Zhang: Sichuan University
Yujiang Fan: Sichuan University
Li Qiu: Sichuan University
Chong Cheng: Sichuan University

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract To mitigate the necessity for multiple invasive procedures in treating malignant osteosarcoma, an innovative therapeutic approach is imperative to achieve controllable tumor-killing effects and subsequent bone repair. Here, we propose the de novo design of sono-activable and biocatalytic nanoparticles-modified 3D-printed hydroxyapatite (HA) scaffold (HS-ICTO) for intelligently sequential therapies in osteosarcoma eradication and bone defect regeneration. The engineered HS-ICTO scaffold displays superior, spatiotemporally controllable H2O2-catalytic performances, which promptly generate massive reactive oxygen species via multienzyme-like mechanisms coupled with sono-activation, thus augmenting tumor cell apoptosis. Furthermore, HS-ICTO can intelligently switch to catalyze H2O2 to O2 within the inflammatory bone defect microenvironment, effectively blocking endogenous H2O2-mediated oxidative stress, which positively modulates the osteogenic differentiation of stem cells and ultimately facilitates defect regeneration. We validate that this multifaceted HS-ICTO scaffold possesses robust and on-demand abilities to prevent neoplastic recurrence and promote anti-inflammatory osseous tissue repair, representing a promising platform for precision oncological intervention and regenerative medicine.

Date: 2025
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DOI: 10.1038/s41467-025-61377-x

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