Work

Microneedle-mediated co-delivery of biomimetic melanin and pro-regenerative factors for oxidative and immune modulation in vitiligo

Year: 2026

Type: article

Abstract: Vitiligo lesions are characterized by elevated epidermal oxidative stress, cytotoxic immune activation, and impaired melanogenesis, while conventional topical therapies often fail to modulate these pathogenic events due to limited skin penetration and therapeutic depth. To address these challenges, a dual-layer gelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA)//hyaluronic acid (HA) (Gel//HA) microneedle system was engineered. The inner HA layer rapidly dissolves upon insertion, releasing keratinocyte-membrane-coated artificial melanin nanoparticles (MPDA) to achieve early reactive oxygen species (ROS) scavenging and targeted delivery to keratinocytes. The outer Gel hydrogel layer enables sustained intradermal delivery of basic fibroblast growth factor (bFGF) and tyrosinase (TYR), supporting melanocyte survival and restoring melanin synthesis. The microneedles exhibited robust mechanical strength (0.234 ± 0.014 N/needle) with a penetration depth of approximately 300-350 μm. In vitro , the cumulative release of bFGF and TYR reached 65% and 70% within the first 72 h, respectively, and subsequently increased more gradually to 92.1% and 90.7% by day 21. In vitro , the combined administration of MPDA, bFGF, and TYR, mitigated H 2 O 2 -induced oxidative injury and enhanced keratinocyte viability. In a monobenzone-induced mouse model, Gel@bFGF/TYR//HA@MPDA treatment markedly promoted repigmentation, restored epidermal melanin deposition, and reduced the expression of CD8, IFN-γ, and TNF-α. Transcriptomic analysis further revealed suppression of ferroptosis-related genes and reactivation of the Wnt–Frizzled–MITF melanogenic signaling axis. This spatially designed microneedle system provides coordinated antioxidant, immunomodulatory, and pro-melanogenic effects, offering a promising localized therapeutic strategy for vitiligo.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2026.103757