ALN-modified MnO_2-x/PEEK implant for bone-targeted catalytic therapy in postoperative osteosarcoma repair

The complex post-surgical management of osteosarcoma requires innovative strategies that can both prevent tumor recurrence and promote bone regeneration. Here, we developed the first MnO_2-x nanoflower decorated polyetheretherketone (PEEK) implant system for “on-demand” therapy, responsive to the elevated H₂O₂ levels and acidic pH of the tumor microenvironment (TME). The PEEK implant surface was engineered by anchoring alendronate sodium (ALN)-loaded MnO_2-x nanoflowers (ALN/MnO_2-x) through hydrophobic interactions and π–π stacking (namely, Mn/A-P implant). In the TME, the elevated H₂O₂ triggers cleavage of boronate esters, releasing ALN/MnO_2-x while the acidic conditions accelerate MnO_2-x dissolution, releasing Mn²⁺ ions. These ions initiate Fenton-like reactions, generating hydroxyl radicals (•OH) that selectively kill tumor cells. In vitro osteogenic assays confirmed that the Mn/A-P system significantly enhances osteoblast differentiation. Further in vivo studies demonstrated that the implant not only eradicates tumor cells through activation of the cGAS-STING pathway, but also markedly promotes new bone formation by upregulating the expression of osteogenic markers including BMP-2, OCN, OPN, and Runx2. This new multifunctional PEEK platform represents a major advance in bone tumor therapy by integrating catalytic tumor therapy with enhanced bone regeneration, offering a promising strategy adaptable to a wide range of orthopedic implant applications in oncology and regenerative medicine.