Immunometabolic cues recompose and reprogram the microenvironment around implanted biomaterials.

Area of Science:

• Biomaterials Science
• Immunology
• Metabolic Engineering

Background:

• Immune cells, including monocytes and neutrophils, infiltrate tissues around biomaterials.
• Chemokine receptors like CCR2 and CX3CR1 are crucial for immune cell trafficking and activation states.
• The biomaterial microenvironment significantly impacts local immune responses and tissue regeneration.

Purpose of the Study:

• To investigate how immunometabolic cues within biomaterial microenvironments regulate immune cell trafficking and function.
• To elucidate the role of chemokine receptors (CCR2, CX3CR1) in immune cell composition and activation.
• To determine if modulating immunometabolism can promote a pro-regenerative microenvironment.

Main Methods:

• Utilized amorphous and crystalline polylactide implants.
• Manipulated cellular metabolism, specifically glycolytic inhibition.
• Analyzed immune cell populations (macrophages, dendritic cells, T cells) and their activation states.
• Assessed chemokine receptor expression (CCR2, CX3CR1) and cytokine production (IL-4).

Main Results:

• Immunometabolic cues, dependent on CCR2 and CX3CR1, govern immune cell trafficking and microenvironment composition.
• Glycolytic inhibition in amorphous polylactide implants promoted a pro-regenerative state via myeloid cells.
• In crystalline polylactide implants, arginase-1 expressing myeloid cells, T helper 2 cells, and γδ+ T cells shaped a pro-regenerative microenvironment.

Conclusions:

• Local metabolic states are key regulators of inflammatory and regenerative processes in biomaterial settings.
• Targeting immunometabolism offers a strategy to engineer biomaterial microenvironments for enhanced tissue regeneration.
• Understanding immune cell dynamics and metabolic reprogramming is critical for designing next-generation biomaterials.