Materiobiomodulated ROS Therapy for De Novo Hair Growth

Hair loss is characterized by the inability of hair follicles (HFs) to enter the telogen-anagen transition (TAT) and lack of de novo HFs. Current pharmaceutical therapies and surgical modalities have been largely limited to regulating hair regrowth efficiently without side effects and lacking treatment compliance. Here, this work proposes a materiobiomodulation therapy (MBMT), wherein polydopamine (PDA) nanoparticles with redox activity can be modulated to have a stoichiometric ROS (H2O2) donating ability. These nanoparticles can intracellularly deliver ROS with high-efficiency via the clathrin-dependent endocytosis process. Utilizing homozygote transgenic HyPerion (a genetically-encoded H2O2 biosensor) mice, this work also achieves in vivo dynamic monitoring of intracellular H2O2 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 beta-catenin-dependent Wnt signaling, upregulating hair follicle stem cell expression. This work further develops 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 study presents a materiobiomodulation therapy using polydopamine nanoparticles for controlled ROS delivery in hair regrowth, utilizing Hyperion mice with an H2O2 biosensor for in vivo ROS monitoring and activation of beta-catenin dependent Wnt signaling in hair follicle stem cells, enabled by a microneedle patch for hair loss treatment. image