Hafnium Oxide Nanostructure-Integrated Silk Fibroin Microneedles Reshape Cutaneous Melanocyte Microenvironment for Vitiligo Therapy

Vitiligo is an autoimmune depigmentary disorder with patchy skin depigmentation, leading to a severe psychosocial burden, but it lacks effective therapeutic options. Melanocyte loss, primarily driven by adaptive immune activation and excessive reactive oxygen species (ROS), is regarded as the central feature of vitiligo. Here, we developed a silk fibroin/poly(vinyl alcohol) microneedle (MN) integrated with α-aminoxyacetate (AOA)-loaded HfO 2 nanoparticles (AH-MNs) for transdermal vitiligo therapy. HfO 2 is expected to protect the cells from ROS damage, while AOA upregulated regulatory T cells (Tregs) and suppressed cytotoxic CD8 + T cell activation in the melanocyte microenvironment simultaneously. The mechanically optimized MNs ensured efficient skin penetration and biocompatible nanoparticle delivery. Benefiting from the ROS scavenging and immune modulation, AH-MNs significantly enhanced melanogenesis, hair follicle activation, and skin repigmentation. Cutaneous tissue analyses revealed attenuation of local autoreactive CD8 + T cells by increased CD4 + FOXP3 + Tregs and reduced IFN-γ-producing CD8 + T cells. Totally, this minimally invasive microneedle strategy offers a promising therapeutic approach for future vitiligo treatment.