Hosung Choi

Background: Transdermal delivery of hydrophilic peptides such as GHK remains limited by the stratum corneum barrier and the classical 500 Da rule. Spicule‐based systems and redox‐responsive linkages have been investigated as strategies to enhance epidermal delivery, but in vivo glutathione‐triggered cleavage remains a proposed mechanism rather than a clinically proven process. Objectives: This study aimed to evaluate the clinical efficacy and safety of a GHK‐conjugated spicule regimen and to determine whether adding a multi‐ingredient, glutathione‐containing booster provides incremental aesthetic benefit compared with the shared base regimen alone. Methods: In this prospective, active‐controlled split‐face clinical trial, 20 healthy Asian women received five weekly facial treatments. One prespecified facial side received the base regimen consisting of a GHK‐conjugated spicule system and base concentrate, while the contralateral side received the same base regimen plus a separate multi‐ingredient booster containing 1% glutathione. Wrinkle depth, pore parameters, skin elasticity, dermal density, surface roughness, and pigmentation were evaluated at baseline, after one and three treatment sessions, and 4 weeks after the fifth session. Between‐side comparisons were performed using change‐from‐baseline values, with prespecified primary endpoints, multiplicity adjustment, and effect‐size reporting. Results: Both sides showed improvements from baseline. At the final timepoint, the intensive regimen produced greater improvements than the base regimen in periorbital wrinkle depth (−0.0144 vs. −0.0084 mm), nasolabial wrinkle depth (−0.0227 vs. −0.0173 mm), dermal density (+7.27 vs. +4.49), roughness (−1.23 vs. −0.73 μm), and mean pore volume (−0.0007 vs. −0.0005 mm ³ ). Multiplicity‐adjusted between‐side differences remained significant for the prespecified primary endpoints and secondary endpoints. No adverse effects were reported. Conclusion: The GHK‐conjugated spicule base regimen improved multiple facial aging indicators, and the booster‐inclusive intensive regimen produced statistically greater short‐term improvements in this small split‐face trial. Because the booster was multi‐ingredient and the release mechanism was not directly measured in vivo, these findings should be interpreted as regimen‐level clinical evidence rather than proof of glutathione‐specific redox cleavage. Trial Registration: TRN Registration Number: PRE20250909‐005

Skin barrier dysfunction and pruritus, central to inflammatory dermatoses, are closely associated with impaired epidermal structural proteins and persistent inflammatory signaling. To address these pathological features, this study aimed to explore the potential anti-inflammatory, barrier-restorative, and anti-pruritic effects of DualPep-ATO, a human-derived cell-penetrating peptide (CPP), using integrated in vitro, ex vivo, and exploratory clinical approaches. Allergic and inflammatory responses were evaluated in rat basophilic leukemia cells and lipopolysaccharide-stimulated macrophages, while barrier-repair properties were partially assessed in ultraviolet B (UVB)-irradiated human epidermal keratinocytes and ex vivo human skin tissue. Mechanistically, DualPep-ATO exhibited no cytotoxicity and successfully suppressed β-hexosaminidase release, nitric oxide production, and pro-inflammatory cytokine expression. Furthermore, it contributed to mitigating skin barrier damage by restoring key epidermal structural proteins, specifically filaggrin, loricrin, and involucrin. Translating these findings clinically, a four-week topical application of a DualPep-ATO cream in adults with compromised skin significantly decreased transepidermal water loss and itch severity. With high participant satisfaction and no reported adverse events, this peptide may serve as a promising peptide-based topical strategy for inflammatory skin conditions associated with barrier dysfunction and pruritus.

Sponge spicules have emerged as promising biomaterial scaffolds due to their biocompatibility and unique structural properties; however, achieving stable and bioactive functionalization remains a key challenge. The tripeptide GHK is known to promote collagen synthesis and wound repair, yet its therapeutic efficacy is often limited by rapid diffusion and instability. Here, we report ALTUM, a thiol-functionalized sponge spicule composite in which GHK is covalently conjugated via disulfide linkage to enable controlled and redox-responsive peptide delivery. ALTUM exhibited sustained GHK retention under physiological and storage conditions, while exposure to reduced glutathione (GSH) selectively accelerated peptide release through disulfide bond cleavage. This dual release behavior—long-term stability combined with reduction-triggered activation—distinguishes ALTUM from conventional delivery systems. The composite also demonstrated structural stability under thermal, cyclic, and photostability conditions. In an artificial human skin model, ALTUM enhanced dermal penetration of GHK and significantly increased collagen deposition in the dermal layer, demonstrating its capacity to promote collagen production within deeper skin tissue, compared to simple spicule–peptide mixtures. ALTUM was fabricated at an optimized spicule-to-peptide ratio of 3% (w/w), preserving the needle-shaped spicule morphology after surface modification. In vitro, ALTUM exhibited a sustained release profile, with GHK release markedly accelerated in the presence of 10 mM glutathione (GSH) compared with non-reductive conditions, reaching approximately 60% cumulative release over 35 days. In the bioprinted artificial human skin model, ALTUM delivered 9.72 ng/cm² of GHK, more than five-fold higher than the physical mixture of spicules and free GHK (1.9 ng/cm²), and significantly increased type I collagen expression in human dermal fibroblasts. Mechanistically, ALTUM-mediated delivery was associated with increased TGF-β expression and engagement of the SMAD signaling pathway, as indicated by increased phosphorylation of SMAD2/3, consistent with involvement of the TGF-β–SMAD axis in the observed collagen induction. Collectively, these findings establish ALTUM as a structurally stable, redox-responsive dermal delivery platform that enhances collagen synthesis and skin regeneration.

Hair aging, a complex physiological process involving progressive hair thinning and loss of luster, is primarily driven by functional decline of hair follicle components and sebaceous glands due to cumulative oxidative stress. This decline manifests as dermal papilla cell (DPC) senescence, with reduced insulin-like growth factor-1 (IGF-1) secretion, impaired hair matrix keratinocyte proliferation, and decreased keratin synthesis. We investigated the restorative potential of poly-D,L-lactic acid (PDLLA) filler, a biostimulatory polymer with antioxidant properties, against these age-related changes. PDLLA filler treatment significantly reduced oxidative stress—as indicated by decreased 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels—in hydrogen peroxide-induced senescent human DPCs, alleviated cell-cycle arrest, and significantly upregulated IGF-1 secretion. Conditioned medium from PDLLA filler-treated DPCs stimulated proliferation and pan-keratin expression in senescent hair follicular keratinocytes (HFKs). Intradermal PDLLA filler injection in aged mice significantly reduced 8-OHdG levels, restored DPC proliferative capacity (indicated by proliferating cell nuclear antigen [PCNA] positivity), increased IGF-1 expression within the dermal papilla, and enhanced HFK proliferation in the hair matrix. Consequently, PDLLA filler treatment robustly upregulated hair cortex keratins (K35, K85) and inner root sheath markers (AE15, K25, K71), leading to improved cuticle integrity and the attenuation of follicular miniaturization. Senescence within sebaceous glands was also mitigated, as evidenced by increased PCNA and peroxisome proliferator-activated receptor gamma (PPAR-γ) expression, accompanied by enhanced hair shaft reflectivity and shine. Overall, PDLLA filler ameliorated senescence-associated phenotypes and restored senescence-associated functional decline, supporting its potential as an intervention for age-related hair thinning and quality deterioration.

Age-associated hair loss is primarily driven by decreased function and proliferation of hair follicle stem cells (HFSCs), often exacerbated by increased inhibitory signaling and changes in the stem cell niche. Macrophage polarization to the anti-inflammatory M2 phenotype is known to increase stem cell proliferation. We investigated the effects of poly-D,L-lactic acid (PDLLA) on hair growth in middle-aged skin, focusing on its role in modulating macrophage polarization and HFSC activity. Senescent macrophages were analyzed for Piezo1 activity, macrophage polarization, and secretion of hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) after PDLLA treatment. Downstream effects on HFSC proliferation, stemness, and Wnt signaling were assessed, including inhibition experiments using the Piezo1 blocker GsMTx4. In vivo analyses assessed hair follicle number, diameter, length, anagen duration, and hair coverage following PDLLA administration in middle-aged mice. PDLLA increased Piezo1 expression and activity in senescent macrophages, enhancing M2 polarization and secretion of HGF and IGF-1. This activated the RAS/ERK signaling pathway, promoting HFSC proliferation and stemness. Furthermore, PDLLA upregulated Wnt signaling molecules (Wnt3a, Wnt10b, and β-catenin) and anagen phase-related factor (Axin2, LEF1, and Lgr5), which were decreased by GsMTX4. In middle-aged animal skin, PDLLA administration led to increased hair follicle number, diameter, and length, as well as prolonged anagen and greater hair coverage. Collectively, these findings suggest that PDLLA rejuvenates the middle-aged skin microenvironment, at least in part through Piezo1-associated M2 macrophage polarization and enhanced HFSC function, offering a promising therapeutic strategy for age-related hair loss targeting both the immune and the stem cell compartments.

Background: Botulinum toxin‐A (BoNT‐A) injection is a widely used cosmetic procedure in Korea to improve calf contours; however, a standardized protocol has yet to be established. While other BoNT‐A formulations have been studied for calf contouring, the efficacy and safety of Inco‐BoNT‐A (IncoBoNT‐A) specifically for this purpose remain unclear. Objective: This prospective case series study aimed to evaluate the effectiveness and safety of IncoBoNT‐A for calf contouring. Methods: Twenty Korean women (mean age: 35.55 ± 7.37) received 75–100 U of IncoBoNT‐A per calf muscle (total 150–200 U for both calves), administered intramuscularly using a 30G 0.5‐inch needle. Evaluations were conducted at baseline and at 1, 3, and 6 months postprocedure. Changes in muscle size were measured via ultrasound and tape, supplemented by clinical photographs. Observer evaluations (PGAIS, Merz scales for female Asian calf) and participant satisfaction (SGAIS) were assessed at each visit, along with body weight monitoring and daily activity assessments. Results: Both calf circumference (measured by tape) and muscle thickness (measured by ultrasound) at 2 fixed locations declined over time, with significant reductions at each visit compared to baseline. The PGAIS and SGAIS scores demonstrated consistent clinical improvement and patient satisfaction. The Merz scale indicated a shift from “severe” and “very severe” to “mild” and “moderate” ratings over time. Notably, weight gain was associated with less reduction in calf circumference. Conclusions: A single dose of 150–200 U IncoBoNT‐A is safe and effective for calf contouring. Unlike facial wrinkle treatment, weight management may be essential for achieving optimal results in calf contouring with BoNT‐A.