3D-Printed Magnesium Peroxide-Incorporated Scaffolds with Sustained Oxygen Release and Enhanced Photothermal Performance for Osteosarcoma Multimodal Treatments

Abstract

The hypoxic microenvironment in osteosarcoma inevitably compromises the antitumor effect and local bone defect repair, suggesting an urgent need for sustained oxygenation in the tumor. The currently reported oxygen-releasing materials have short oxygen-releasing cycles, harmful products, and limited antitumor effects simply by improving hypoxia. Therefore, the PCL/nHA/MgO 2 /PDA-integrated oxygen-releasing scaffold with a good photothermal therapy effect was innovatively constructed in this work to achieve tumor cell killing and bone regeneration functions simultaneously. The material distributes MgO 2 powder evenly on the scaffold material through 3D printing technology and achieves the effect of continuous oxygen release (more than 3 weeks) through its slow reaction with water. The in vitro and in vivo results also indicate that the scaffold has good biocompatibility and sustained-release oxygen properties, which can effectively induce the proliferation and osteogenic differentiation of bone mesenchymal stem cells, achieving excellent bone defect repair. At the same time, in vitro cell experiments and subcutaneous tumorigenesis experiments also confirmed that local oxygen supply can promote osteosarcoma cell apoptosis, inhibit proliferation, and reduce the expression of heat shock protein 60, thereby enhancing the photothermal therapy effect of polydopamine and efficiently eliminating osteosarcoma. Taken together, this integrated functional scaffold provides a unique and efficient approach for antitumor and tumor-based bone defect repair for osteosarcoma treatment.

Hyaluronic Acid-Modified Spherical MgO2/Pd Nanocomposites Exhibit Superior Antitumor Effect through Tumor Microenvironment-Responsive Ferroptosis Induction and Photothermal Therapy

“…Thus, various H 2 O 2 -generating agents have been used to enhancing the intratumoral H 2 O 2 concentrations, such as glucose oxidase, , gold nanoparticles (NPs), and metal peroxides. , Glucose can be catalyzed by glucose oxidase and gold NPs to generate H 2 O 2 under the presence of dissolved oxygen; however, the hypoxia of tumor microenvironment (TME) severely restricts their catalytic efficiency . Promisingly, the metal peroxides seem to be promising alternatives, such as magnesium peroxide (MgO 2 ), calcium peroxide (CaO 2 ), copper peroxide, zinc peroxide, barium peroxide, and titanium peroxide, and these NPs have been widely studied for tumor therapy due to their superior capacity of self-supplying H 2 O 2 in TME without additional requirements. TME-responsive copper peroxide can play as both H 2 O 2 provider and catalysts in triggering Fenton-like reaction, whereas the potential biosafety of Cu ions is a critical issue because of its toxicity to normal cells or tissues at high dose. , Comparatively, MgO 2 and CaO 2 nanoparticles are desirable due to the biocompatibility of Mg 2+ and Ca 2+ that are abundant in vivo.…”

MgSiO3 Fiber Membrane Scaffold with Triggered Drug Delivery for Osteosarcoma Synergetic Therapy and Bone Regeneration

“…However, for magnesium-based and silicon-based ceramic materials, their antiosteosarcoma performance is relatively limited. In some studies, magnesium peroxide has been introduced to achieve the production of hydrogen peroxide and oxygen in a physiological environment, promoting the apoptosis of osteosarcoma cells and inhibiting proliferation. , Additionally, Liang et al fabricated a 3D-printed silicene bioactive glass scaffold to achieve PTT for inhibiting osteosarcoma, and because of the release of bioactive elements during degradation, it possesses outstanding osteogenic biological functionality. Furthermore, by introducing transition metal elements or preparing composite materials, more treatments have been endowed with antiosteosarcoma properties such as ion anticancer, cuproptosis, and chemodynamic therapy (CDT) …”