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Multi-Scale Modification of Metallic Implants With Pore Gradients, Polyelectrolytes and Their Indirect Monitoring In vivo

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Stereochemistry Determines Immune Cellular Responses to Polylactide Implants.

Chima V Maduka^1,2,3, Mohammed Alhaj⁴, Evran Ural^2,3

¹Comparative Medicine & Integrative Biology, Michigan State University, East Lansing, Michigan 48824, United States.

ACS Biomaterials Science & Engineering

|January 12, 2023

Summary

Polylactide (PLA) stereochemistry significantly influences immune responses. Different PLA types trigger distinct inflammatory pathways, highlighting the role of immunometabolism in biomaterial biocompatibility.

Keywords:

biocompatibility biomaterials immune cells immunometabolism polylactide stereochemistry

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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.