<i>Cinnamomum burmannii</i> Leaves-Derived Carbon Dots Promote Angiogenesis and Stimulate Hair Follicle Regeneration by Reshaping the Microenvironment of Hair Follicles

Androgenic alopecia (AGA) is a prevalent chronic inflammatory disease with limited effective treatment. <i>Cinnamomum burmannii</i> (<i>C. burmannii</i>) is a traditional Asian herbal medicine. Its components have anti-inflammatory, analgesic, and transmembrane absorption effects. Previous studies have reported that <i>Cinnamomum osmophloeum</i> can promote hair growth; however, there are limitations of poor solubility and low bioavailability, necessitating the development of more biocompatible, safer, and more effective treatment strategies. Here, we developed a novel method for carbon dots derived from <i>C. burmannii</i> leaves (Cb-CDs) to remodel the hair follicle microenvironment through synergistic dual mechanisms of reactive oxygen species (ROS) scavenging, reducing inflammatory damage, inhibiting apoptosis, and promoting proliferation, as well as activating core effectors of the Wnt pathway. In vitro experiments revealed that Cb-CDs inhibited DPPH free radicals by 93.91%, exhibited notable superoxide dismutase (SOD)-like activity, and exhibited high transdermal permeability with penetration depth of 200 μm. Subsequent in vivo zebrafish experiments further confirmed the anti-inflammatory activity of Cb-CDs, which could significantly inhibit neutrophil migration, and the inhibition rate was 90.91%. In the AGA mouse model, 0.05% Cb-CDs increased hair regeneration coverage to 87.11% and regrowth hair diameter significantly thickened. Additionally, there was a 1.95-fold increase in Ki67 cell proliferation, a 3.1-fold rise in VEGF vessel density, and Cb-CDs removed ROS to lessen inflammation and change macrophage polarization to a pro-inflammatory phenotype. In terms of mechanism, Cb-CDs may remodel the hair follicle microenvironment by inhibiting the TGF-β1 and NF-κB p65 signaling pathway while activating the β-catenin (the core molecule of the Wnt pathway) and Cycline D1 signaling pathway. This multifaceted action stimulates cell proliferation and angiogenesis, reduces oxidative stress and inflammation, and prolongs the anagen phase. Therefore, this study proposes a new strategy of "multifunctional activated biomass carbon dot" for AGA treatment.