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Published on: January 7, 2020
Macrophage microRNA-146a is a central regulator of the foreign body response to biomaterial implants
Abstract:
Host recognition and immune-mediated foreign body response (FBR) to biomaterials can adversely affect the functionality of implanted materials. To identify key targets underlying the generation of FBR, here we perform analysis of microRNAs (miR) and mRNAs responses to implanted biomaterials. We found that (a) miR-146a levels inversely affect macrophage accumulation, foreign body giant cell (FBGC) formation, and fibrosis in a murine implant model; (b) macrophage-derived miR-146a is a crucial regulator of the FBR and FBGC formation, as confirmed by global and cell-specific knockout of miR-146a; (c) miR-146a modulates genes related to inflammation, fibrosis, and mechanosensing; (d) miR-146a modulates tissue stiffness near the implant during FBR; and (e) miR-146a is linked to F-actin production and cellular traction force induction, which are vital for FBGC formation. These novel findings suggest that targeting macrophage miR-146a could be a selective strategy to inhibit FBR, potentially improving the biocompatibility of biomaterials.
Insights
MicroRNA-146a (miR-146a) is key in regulating the foreign body response (FBR) to biomaterials. Targeting macrophage miR-146a can inhibit FBR and improve implant biocompatibility.
Area of Science:
- Biomaterials Science
- Immunology
- Molecular Biology
Background:
- Host recognition and immune responses to biomaterials can impair implant function.
- The foreign body response (FBR) is a critical challenge in biomaterial development.
- Understanding the molecular mechanisms of FBR is essential for improving biomaterial biocompatibility.
Approach:
- Analysis of microRNA (miR) and mRNA expression in response to implanted biomaterials.
- Utilized a murine implant model to study FBR.
- Employed global and cell-specific knockout of miR-146a in macrophages to confirm its regulatory role.
Key Points:
- miR-146a levels inversely correlate with macrophage accumulation, foreign body giant cell (FBGC) formation, and fibrosis.
- Macrophage-derived miR-146a is a critical regulator of FBR and FBGC formation.
- miR-146a influences genes involved in inflammation, fibrosis, and mechanosensing, impacting tissue stiffness and cellular mechanics (F-actin production, traction force).
Conclusions:
- Macrophage miR-146a is a pivotal regulator of the foreign body response.
- Modulating macrophage miR-146a offers a targeted strategy to mitigate FBR.
- Inhibiting miR-146a may enhance the biocompatibility of implanted biomaterials.
