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Novel strategy combats implant-associated infections by starving bacteria while sparing healthy cells

A research team led by Prof. Liu Xuanyong from the Shanghai Institute of Ceramics of the Chinese Academy of Sciences has introduced a pioneering antibacterial strategy that disrupts bacterial energy metabolism by interfering with proton and electron transfer in bacterial membranes.

Their findings, in Science Advances and featured as a cover paper, present a groundbreaking concept: selective antibacterial starvation therapy, offering a promising solution for implant-associated infections.

Infections, particularly those associated with implants, pose a significant postoperative challenge, since bacteria within biofilms on implants can evade antibiotic treatments. Conventional antibacterial approaches—such as metal-based agents and reactive oxygen species generation—often struggle to selectively eliminate bacteria while preserving the viability of healthy cells. This challenge has driven researchers to develop innovative strategies that target bacterial survival mechanisms without harming cells and tissues.

The team's novel approach focuses on disrupting bacterial energy metabolism through a Schottky heterojunction film composed of gold and alkaline magnesium-iron mixed metal oxides on titanium implants. When bacteria come into contact with the film, the heterojunction captures protons and electrons from the bacterial respiratory chain, leading to energy depletion and severe oxidative stress. This disruption inhibits ATP synthesis and other essential biosynthetic processes, ultimately causing bacterial death due to DNA and membrane damage.

Importantly, this heterojunction film does not affect mammalian cells, since their energy metabolism occurs within intracellular mitochondria, which are shielded from direct extracellular interference. The material's selective antibacterial efficacy was confirmed in rat osteomyelitis and mouse percutaneous infection models, demonstrating both biosafety and the capacity to kill bacteria while supporting tissue integration. This breakthrough highlights a significant advancement in the development of antibacterial biomaterials that can effectively target bacteria while preserving healthy cells.

Beyond its immediate application, the study underscores the broader potential of disrupting bacterial energy metabolism. Similar antibacterial effects were observed in other heterojunction systems, suggesting that further optimization—such as refining the size, distribution, and composition of metal nanoparticles and mixed metal oxides—could enhance biological performance.

"This study provides a new perspective on designing biosafe antibacterial biomaterials," said Prof. Liu. "By interfering with proton and electron transfer, we can selectively target bacteria without harming healthy cells, offering a promising strategy for combating implant-associated infections."

These findings contribute to the development of smart biomaterials that can precisely regulate biological processes, potentially transforming infection treatments and improving implant safety. The team's work addresses a critical medical challenge while paving the way for next-generation biomedical materials that control biological behaviors at the molecular level.

This breakthrough has the potential to transform infection management and enhance the long-term performance of biomedical implants, ultimately benefiting patients worldwide.