Daily Cosmetic Research Analysis

Stem cells and their paracrine factors hold promise for alopecia treatment, yet research on human skin-derived precursors (hSKPs), which are closely related to hair follicles in biological positioning and function, remains limited. We demonstrated that extracellular vesicles of human transformed skin-derived precursors (htSKP-EVs), harvested utilizing our directed induction, culture transition and gradient ultracentrifugation technology, exhibited superior efficiency and quality determined by transmission electron microscopy, nanoparticle tracking analysis, and detection of specific markers. Using CCK8, scratch assay, immunofluorescence, H&E staining, immunohistochemistry staining, dermoscope, qRT-PCR and Western blotting, it was found that htSKP-EVs significantly promoted the proliferation of hair follicle stem cells (hHFSCs) by effectively modulating the Wnt signaling pathway, thereby enhancing overall hair follicle growth. Notably, miR-221-3p, highly expressed in htSKP-EVs, suppressed DKK2 expression, activated the Wnt pathway in human dermal papilla cells (hDPCs), and induced hair follicles to enter and sustain the anagen phase, based on the aforementioned similar in vivo and in vitro experiments. These findings, validated in hHFSCs, hDPCs and human hair follicles in vitro and in a murine alopecia model in vivo, revealed the potential mechanism of htSKP-EVs in hair growth and identified a new therapeutic target for alopecia in regenerative medicine.

Topical and transdermal drug and cosmetic development is advancing across industry; however, the efforts may in part be hindered by paucity of data on the fate of chemicals in human skin, which depend on protein-mediated transport and biotransformation of such chemicals. A label-free mass spectrometry-based proteomics approach was used to comprehensively quantify drug metabolizing enzymes and transporters in the fractionated epidermis and dermis of 17 healthy Caucasian human skin samples. Over 1000 proteins were identified for cytosolic and membrane components, and abundance were obtained using a modified HiN (high 3/2 ion intensity) approach (without using standards). Key findings included high interindividual variability in the expression of phase I and II enzymes (eg, aldehyde dehydrogenase 2, carboxylesterase 1, glutathione S-transferase P1, and glutathione peroxidase 3) and solute carrier transporters (eg, SLC25A5, SLC25A6). Notably, several metabolic enzymes, previously uncharacterized in human skin, were quantified in the membrane fractions, including glutathione S-transferases (GSTs) such as GSTM3 (12.2 pmol/mg protein) and GSTP1 (5.55 pmol/mg protein). Subcellular localization analysis revealed that many quantified proteins were associated with mitochondrial or membrane compartments, reinforcing the functional diversity and compartmentalized nature of dermal metabolism. Furthermore, strong correlations in enzyme and transporter expression were observed between the dermis and epidermis (Spearman's ρ > 0.85). This dataset provides the most detailed quantification to date of drug metabolizing enzymes and transporters in human skin and offers critical input parameters for dermal physiologically based pharmacokinetic modeling applications. These quantitative insights improve the accuracy and clinical relevancy of in vitro in vivo extrapolations related to dermal drug metabolism and disposition for chemicals applied to the skin or those that come into contact with the skin inadvertently. Integration of this proteomic dataset into physiologically based pharmacokinetic frameworks will enhance the scientific reliability, applicability across product applications and regulatory acceptance of skin-based models for drug development and safety evaluation. SIGNIFICANCE STATEMENT: Understanding drug metabolism and transport in human skin is essential for predicting dermal absorption and safety. This study provides the most comprehensive proteomic dataset of metabolizing enzymes and transporters in epidermis and dermis, revealing high interindividual variability, previously unquantified enzymes, and strong layer correlations, supporting improved dermal physiologically based pharmacokinetic model development.

Effective and controlled mechanical wound closure is essential for preventing infection, promoting re-epithelialization, and minimizing scarring. However, existing wound closure technologies are limited to uniaxial closures and lack programmability, which hinders their adaptability to wounds with complex morphologies and restricts personalized treatment needs. Here, we propose a multiaxial stretchable wound zipper engineered from electrothermally driven mechanical metamaterials. The device features a hierarchical lattice of shape memory alloys, enabling six axes of stretching and programmable contraction via a smartphone. It delivers adjustable contraction force ranging from 0 to 0.494 MPa, adaptable to diverse wound geometries, with a rapid response time of approximately 1.73 s. In the rat model, the device achieved near-instantaneous closure of linear wounds and improved the circular wound-healing rate by 35.91% compared with the control group. Mechanistically, the programmable mechanical contraction promoted vascular regeneration, re-epithelialization, and collagen matrix remodeling, ultimately accelerating personalized wound healing. The device achieved rapid, robust, and programmable multiaxial contraction, demonstrating substantial potential for personalized wound management and clinical translation.