Persistent glycolysis defines pathological foreign body-associated inflammation to polymeric implants

Area of Science:

• Biomaterials Science
• Immunology
• Cellular Metabolism

Background:

• Nondegradable polymeric medical devices can cause persistent inflammation and fibrosis.
• This peri-implant inflammation involves activated macrophages with profibrotic behavior.
• Macrophage metabolic regulation in this context is largely unexplored.

Purpose of the Study:

• To investigate the metabolic dependence of macrophages in peri-implant inflammation.
• To explore the role of glycolysis in macrophage activation and profibrotic behavior.
• To identify potential metabolic targets for mitigating implant-associated fibrosis.

Main Methods:

• Ex vivo profiling of metabolic dependence and capacity in peri-implant tissues.
• Analysis of glucose transporter 1 (GLUT1) expression.
• Transcriptomic assessment of macrophage populations.
• Correlation of metabolic profiles with cellular behavior and gene expression.

Main Results:

• Macrophages in peri-implant tissues showed persistent reliance on glycolysis up to 6 weeks postimplantation.
• Glucose transporter 1 (GLUT1) expression increased with time and proximity to the implant.
• Glycolytic dependence was pronounced in multinucleated macrophages, associated with phagocytic activity.
• Upregulation of pathological wound healing pathways correlated with high glucose import capacity.

Conclusions:

• Glycolysis is a definitive metabolic system driving persistent peri-implant inflammation.
• Targeting macrophage glycolysis presents a potential strategy to reduce fibrosis around medical implants.
• Understanding cellular metabolism is crucial for developing advanced biomaterials.