Endogenous Glucose/pH Dual‐Responsive PEEK Implant With Cascade‐Amplified Antibacterial and Osteogenic Activities for Infected Diabetic Bone Defects

ABSTRACT Hyperglycemia in diabetics compromises bone defect repair by elevating infection risks and suppressing osteogenesis. Although polyetheretherketone (PEEK) possesses suitable mechanical properties and biocompatibility, the intrinsic bioinertness constrains its therapeutic efficacy in diabetics. Herein, we developed an antibiotic‐free, glucose/pH dual‐responsive PEEK implant that exclusively leverages endogenous conditions to trigger cascade‐amplified therapeutic effects. This design features co‐immobilization of synthesized copper‐tannic acid nanoparticles (CuTANps) and glucose oxidase (GOx) onto a porous sulfonated PEEK surface. In this system, GOx catalyzes glucose to produce H ₂ O ₂ and gluconic acid. The resulting acidic environment (comprising both the inherent acidity of the bacterial infection and accumulated gluconic acid) induces the dissociation of CuTANps. The released Cu ² ⁺ is then reduced to Cu⁺ by TA and intracellular glutathione, which subsequently reacts with H ₂ O ₂ via a Fenton‐like reaction to generate highly reactive hydroxyl radicals, enabling amplified antibacterial effects. The optimized PEEK achieves killing rates exceeding 98% against drug‐resistant Gram‐positive/‐negative bacteria in vitro. Correspondingly, this implant reduced bacterial colonization by over 97% in vivo, while the synergistic effect of Cu ² ⁺ and the porous sulfonated surface further enhanced osseointegration, yielding approximately 1.5‐fold increase in bone volume fraction compared to pristine PEEK. Together, this study developed an endogenous stimuli‐responsive PEEK implant tailored for the infected diabetic bone defects microenvironment, which achieves cascade‐amplified antibacterial and osteogenic therapies.