Local Immunomodulation Using an Adhesive Hydrogel Loaded with miRNA-Laden Nanoparticles Promotes Wound Healing

Area of Science:

• Biomaterials Science
• Immunology
• Regenerative Medicine

Background:

• Chronic wounds exhibit impaired healing and inflammation, hindering immune function and increasing infection risk.
• MicroRNAs (miRNAs), specifically miR-223, can promote anti-inflammatory macrophage polarization (M2 phenotype), potentially accelerating wound healing.
• Challenges in miRNA therapy include their low stability and difficulty in targeted local delivery.

Purpose of the Study:

• To develop adhesive hydrogels loaded with hyaluronic acid nanoparticles containing miR-223 5p mimic (miR-223*) for controlled macrophage polarization.
• To investigate the in vitro and in vivo therapeutic potential of this novel delivery system for wound healing.

Main Methods:

• Development of adhesive hydrogels incorporating miR-223*-loaded hyaluronic acid nanoparticles.
• In vitro assessment of miR-223* effects on macrophage polarization using J774A.1 cells, analyzing inflammatory and anti-inflammatory gene markers (Arg-1, TNF-α, IL-1β, IL-6).
• In vivo evaluation in an acute excisional wound model, assessing hydrogel adhesion, wound healing, vascularization, and macrophage polarization via histological and qPCR analyses.

Main Results:

• In vitro studies confirmed miR-223* upregulation induced M2 macrophage polarization, increasing Arg-1 and decreasing TNF-α, IL-1β, and IL-6.
• In vivo, the adhesive hydrogels effectively covered wounds and promoted uniform, vascularized skin formation.
• Histological and qPCR analyses confirmed efficient local delivery of miR-223* promoted M2 macrophage polarization, leading to accelerated wound healing.

Conclusions:

• Nanoparticle-laden hydrogels effectively deliver miR-223* for targeted control of macrophage polarization.
• This therapeutic strategy shows significant potential for accelerating chronic wound healing through enhanced tissue regeneration and vascularization.