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A Macrophage Reporter Cell Assay to Examine Toll-Like Receptor-Mediated NF-kB/AP-1 Signaling on Adsorbed Protein Layers on Polymeric Surfaces
Published on: January 7, 2020
Masking macrophage injury sensing via poly I sustained release system reduces inflammation and fibrosis
Keyi Chen1, Xingjian You1, Wei Yu2
1Spine Center, Department of Orthopedics, Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Abstract:
Tissue fibrosis following injury often leads to severe complications in humans. Recent research highlights that macrophage hypermigration and activation play a critical role in fibrosis development. Emerging evidence suggests that macrophage sensing of tissue injury via damage-associated molecular patterns (DAMPs) is crucial for their migration and activation. Excessive injury sensing is linked to macrophage hyperactivity, aberrant inflammation, and fibrosis. Recent studies have shown that polyinosinic acid (Poly I) can reduce macrophage activation by inhibiting signaling pathway associated with macrophage scavenger receptors (MSR). Based on this, we developed an electrospun polycaprolactone (PCL) fibrous membrane incorporating Poly I (PCL-Poly I) to ensure its early sustained release and function as an effective physical barrier. In vitro and in vivo results showed that Poly I could mask macrophage early injury sensing by downregulating MSR1/PI3K/AKT/SPP1 pathway. The local implantation of PCL-Poly I could reduce the early aggregation and activation of macrophages in the epidural fibrosis (EF) zone, thus suppressing the fibroblast activation and EF progress, with its therapeutic efficacy lasting up to 8 weeks after laminectomy. In conclusion, this study demonstrates the potential of biomaterial-based strategies to modulate immune responses, offering a novel upstream solution for treating fibrosis-related conditions.
Insights
This study developed a biomaterial (PCL-Poly I) to reduce macrophage activation and injury sensing, effectively suppressing tissue fibrosis development and offering a novel treatment strategy for fibrosis-related conditions.
Area of Science:
- Biomaterials Science
- Immunology
- Regenerative Medicine
Background:
- Tissue fibrosis is a significant complication following injury, driven by excessive macrophage activity.
- Macrophage sensing of tissue injury via damage-associated molecular patterns (DAMPs) is critical for their activation and migration.
- Inhibiting macrophage scavenger receptors (MSR) with polyinosinic acid (Poly I) can reduce activation.
Purpose of the Study:
- To develop a sustained-release biomaterial incorporating Poly I for treating epidural fibrosis (EF).
- To investigate the efficacy of Poly I in modulating macrophage responses to tissue injury.
- To assess the therapeutic potential of PCL-Poly I in suppressing fibroblast activation and EF progression.
Main Methods:
- Development of an electrospun polycaprolactone (PCL) fibrous membrane incorporating Poly I (PCL-Poly I).
- In vitro and in vivo studies to evaluate Poly I's effect on macrophage signaling pathways (MSR1/PI3K/AKT/SPP1).
- Local implantation of PCL-Poly I in an epidural fibrosis model following laminectomy.
Main Results:
- Poly I effectively masked early macrophage injury sensing by downregulating the MSR1/PI3K/AKT/SPP1 pathway.
- PCL-Poly I implantation reduced early macrophage aggregation and activation in the EF zone.
- Fibroblast activation and EF progression were suppressed, with therapeutic effects lasting up to 8 weeks.
Conclusions:
- Biomaterial-based strategies can effectively modulate immune responses to treat fibrosis.
- PCL-Poly I offers a novel upstream therapeutic approach for fibrosis-related conditions by targeting early macrophage sensing.
- This study highlights a promising strategy for managing tissue fibrosis and its complications.
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