Stereochemistry Determines Immune Cellular Responses to Polylactide Implants

Area of Science:

• Biomaterials Science
• Immunology
• Biochemistry

Background:

• Polylactide (PLA) stereochemistry impacts its properties and clinical performance.
• PLA degradation can cause inflammation and fibrosis, but stereochemistry's role is unclear.
• In vitro models are needed to understand differential immune responses to various PLA stereochemistries.

Purpose of the Study:

• To investigate immune cellular responses to different PLA stereochemistries using a bioenergetic model.
• To elucidate the mechanistic links between PLA degradation products and immune cell metabolism.
• To explore the role of immunometabolism in PLA biomaterial biocompatibility.

Main Methods:

• Applied a bioenergetic model to study immune responses to PLLA, PDLA, and stereocomplex PLA.
• Analyzed cytokine protein levels (IL-1β, TNF-α, IL-6, MCP-1, IL-10) in response to PLA degradation products.
• Investigated metabolic changes (glycolysis, oxidative phosphorylation) in macrophages and fibroblasts.

Main Results:

• Stereocomplex PLA breakdown increased IL-1β, TNF-α, and IL-6 via glycolysis in macrophages.
• PLLA and PDLA degradation products selectively increased MCP-1.
• PDLA increased both glycolysis and oxidative phosphorylation, while PLLA increased only oxidative phosphorylation.
• Glycolytic inhibition reduced pro-inflammatory cytokines and increased IL-10.

Conclusions:

• PLA stereochemistry dictates distinct immunometabolic responses in macrophages and fibroblasts.
• Mechanistic insights into PLA-induced inflammation are provided by immunometabolism.
• Targeting cellular metabolism may enhance the biocompatibility of PLA biomaterials.