Cellular and microenvironmental cues that promote macrophage fusion and foreign body response

Area of Science:

• Biomaterials Science
• Cell Biology
• Immunology

Background:

• The foreign body response (FBR) involves macrophages fusing into foreign body giant cells (FBGCs).
• FBGC formation impacts biomaterial performance and therapeutic delivery, but the underlying microenvironmental cues are unclear.
• Existing research presents conflicting data on factors influencing FBGC development.

Purpose of the Study:

• To identify molecular and cellular factors driving FBGC formation in vitro.
• To elucidate the role of microenvironmental changes and cellular crosstalk in FBGC development.

Main Methods:

• In vitro culture of macrophages to assess fusion competencies.
• Analysis of cytokine and growth factor profiles during microenvironmental transitions.
• Investigation of Toll-like receptor signaling and fibroblast-macrophage interactions.

Main Results:

• Macrophage fusion capacity varied based on monocyte differentiation status.
• FBGC formation correlated with a shift from a proinflammatory to a reparative microenvironment.
• Fibroblast secretomes promoted PDGF secretion by macrophages, enhancing large FBGC formation; Toll-like receptor signaling influenced multinucleated FBGCs but not basic fusion.

Conclusions:

• Monocyte differentiation and fibroblast-macrophage crosstalk are critical regulators of FBGC formation.
• A specific combination of cellular and microenvironmental factors orchestrates effective foreign body responses.
• Findings provide insights into controlling FBGC development for improved biomaterial applications.