Materiobiomodulated ROS Therapy for De Novo Hair Growth

Abstract Hair loss is characterized by the inability of hair follicles to enter the telogen‐anagen transition (TAT) and lack of de novo hair follicles (HFs). Current pharmaceutical therapies and surgical modalities have been largely limited to regulating hair regrowth efficiently without side effects and lacking treatment compliance. Here we propose a materiobiomodulation therapy (MBMT), wherein polydopamine (PDA) nanoparticles with redox activity can be modulated to have a stoichiometric ROS (H 2 O 2 ) donating ability. These nanoparticles can intracellularly deliver ROS with high‐efficiency via the clathrin‐dependent endocytosis process. Utilizing homozygote transgenic HyPerion (a genetically‐encoded H 2 O 2 biosensor) mice, we also achieve in vivo dynamic monitoring of intracellular H 2 O 2 elevation induced by ROS donators. Subcutaneous administration with ROS donators results in rapid onset of TAT and subsequent hair regrowth with a specific ROS “hormesis effect”. Mechanistically, ROS activate β‐catenin‐dependent Wnt signaling, upregulating hair follicle stem cell (HFSC) expression. We further developed a microneedles patch for transdermal ROS delivery, demonstrating long‐term, low‐dose ROS release. Unlike photobiomodulation therapy (PBMT), MBMT requires no external stimuli, providing a convenient and efficient approach for clinical hair loss treatment. This material‐HF communication implicates new avenues in HF‐related diseases, achieving targeted ROS delivery with minimal side effects. This article is protected by copyright. All rights reserved