Metabolism-Guided Lattice Strain Engineering for Eradicating Implant Infections via Bacterial Energy Reprogramming

ABSTRACT:

Bone implant infections are exacerbated by bacterial biofilm formation, where dynamic metabolic transitions create therapeutic vulnerabilities often missed by conventional static or dynamic therapies. Here, we present a metabolism-guided strategy via lattice strain engineering to reprogram bacterial energetics for full-cycle infection eradication. By constructing a compressed lattice in BaTiO3 through Sr-doping and vacancy engineering (BST-epsilon), we establish a persistent electron sink that forcibly extracts electrons from the bacterial respiratory chain. This intervention arrests early-stage proliferation by switching energy production from oxidative phosphorylation to inefficient glycolysis, a mechanism validated by multi-omics analysis showing drastic ATP depletion. Subsequently, ultrasound activation leverages the strain-induced flexoelectric effect to optimize band bending, lowering the water dissociation barrier to generate ROS and O2. The released oxygen revitalizes dormant bacteria within mature biofilms, rendering them susceptible to oxidative damage and disrupting membrane integrity. Concurrently, the sustained release of Sr2+ reverses infection-induced osteolysis by modulating the OPG/RANKL pathway. In rat models, this metabolism-guided platform achieves complete bacterial elimination and enhances osseointegration. This work establishes lattice strain engineering as a universal strategy to bridge static metabolic interference with dynamic catalytic therapy, offering a new paradigm for the full-cycle management of implant infections.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS16097 | MetaboLights | 2026-10-21

REPOSITORIES: MetaboLights