Glucose-gated nanocoating endowing polyetheretherketone implants for enzymatic gas therapy to boost infectious diabetic osseointegration

Abstract

The hyperglycemic micromilieu surrounding implants in diabetic patients leads to high failure rate of implantation and implant-associated infection. Carbon monoxide (CO) has been reported to combat infections; however, its on-demand liberation and the elucidation of the underlying antibacterial mechanism remain challenging. To address this issue, we develop a multipurpose orthopedic implant comprising polyetheretherketone, glucose oxidase (GOx), and manganese carbonyl nanocrystals (MnCO), serving as a glucose-gated nanocoating for enzymatic gas therapy to improve infectious diabetic osseointegration. The GOx acts as a glucose-actuated gate responsive to hyperglycemia, thereby delivering CO in situ triggered by the GOx-driven Fenton-like reaction of MnCO nanocrystals. The released CO considerably prevents bacterial multiplication by penetrating the membrane, binding to cytochrome bo3, and interfering with the respiratory chain in vitro. Furthermore, the engineered implant displays desired antibacterial properties and enhances osseointegration in vivo. Collectively, the orthopedic nanocoating implant is capable of delivering glucose-gated enzymatic gas therapy, promising for treating infectious diabetic bone defects.