Bioorthogonal Click-Engineered Microneedle Patch Enables Adeno-Associated Virus-Mediated Dermal Acidic Fibroblast...

Area of Science:

• Biomaterials Engineering
• Dermatology
• Gene Therapy

Background:

• Hair loss is a common condition with few effective treatments.
• Acidic fibroblast growth factor (aFGF) shows potential for hair regeneration but has poor bioavailability.
• Efficient delivery of therapeutic agents for hair loss remains a challenge.

Purpose of the Study:

• To develop a bioorthogonal click-engineered microneedle patch (ClickMNP) for efficient intradermal delivery of adeno-associated virus encoding aFGF (AAV-aFGF).
• To evaluate the efficacy of ClickMNP in promoting hair regeneration and addressing limitations of protein-based therapies.

Main Methods:

• Synthesized dibenzocyclooctyne-modified hyaluronic acid (HA-DBCO) and azide-functionalized poly(lactide-co-glycolide) (PLGA-N3) microneedles.
• Utilized strain-promoted azide-alkyne cycloaddition (SPAAC) to create a cross-linked hydrogel on the microneedle surface, immobilizing AAV-aFGF.
• Administered ClickMNP intradermally in murine alopecia models and assessed hair regeneration, follicle cycling, and angiogenesis.

Main Results:

• ClickMNP enabled sustained AAV-aFGF expression, overcoming issues of low exposure and rapid clearance.
• A single ClickMNP administration significantly accelerated hair follicle regeneration, enhanced dermal angiogenesis, and prolonged anagen phase in mice.
• The treatment outperformed free AAV-aFGF and recombinant aFGF, preserving follicle viability and promoting native-like follicular architecture.

Conclusions:

• ClickMNP provides a versatile bioorthogonal microneedle-virus interface for gene therapy.
• This strategy offers a transformative solution for hair loss and other cutaneous indications.
• The approach combines chemical engineering with gene therapy for enhanced therapeutic delivery and efficacy.