Thermosensitive Hydrogel Enables Noninvasive Extracellular Vesicle Therapy for Atopic Dermatitis

Area of Science:

• Dermatology
• Biomaterials Science
• Immunology

Background:

• Atopic dermatitis (AD) is a chronic inflammatory skin condition with impaired barrier function and Th2-dominant immune dysregulation.
• Current treatments using mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) require subcutaneous injection, causing pain and limiting patient compliance.

Purpose of the Study:

• To develop a patient-friendly, noninvasive topical delivery system for MSC-EVs to treat atopic dermatitis.
• To evaluate the efficacy of MSC-EVs incorporated into a thermosensitive hydrogel for AD treatment in a preclinical model.

Main Methods:

• Clinical-grade MSC-EVs were incorporated into a hyaluronic acid/Pluronic F127 (HP) thermosensitive hydrogel.
• The optimized HP hydrogel demonstrated shear-thinning properties and sol-gel transition at body temperature for sustained EV release.
• The efficacy of topical HP-loaded EVs (HP+EVs) was assessed in a Dermatophagoides farinae-extract-induced AD mouse model.

Main Results:

• Topical HP+EVs significantly suppressed AD symptoms, epidermal thickening, and mast cell infiltration, comparable to subcutaneous EV injections.
• HP+EV treatment normalized Th2 and Th1/pro-inflammatory cytokine levels.
• EVs penetrated the disrupted skin barrier via surface-protein-dependent mechanisms, up-regulated barrier proteins, and reduced oxidative stress.

Conclusions:

• A noninvasive topical hydrogel formulation (HP+EVs) provides a promising therapeutic strategy for atopic dermatitis.
• This approach overcomes limitations of injection-based delivery, enhancing patient compliance and potentially improving AD management.