Extracellular vesicles (EVs) have gained attention in the cosmetics industry for their role in intercellular communication and tissue regeneration. They transfer bioactive molecules such as proteins, lipids, and nucleic acids, promoting skin repair, rejuvenation, and anti-aging effects. Human mesenchymal stem cell-derived EVs are particularly valued for their ability to enhance collagen production, reduce inflammation, and improve skin texture and hydration. However, their use is prohibited by regulatory agencies. Plant- and bacterial-derived EVs are being explored to meet the demand for innovative cosmetics. Despite their potential, challenges such as regulatory approval, high production costs, and product stability need to be addressed to fully realize the benefits of EV-based cosmetics. This paper examines the mechanisms, benefits, market trends, and prospects of EV-based skincare products, highlighting their transformative impact on the cosmetic industry.

Facial aging is primarily characterized by the loss and disorganization of the dermal extracellular matrix (ECM), particularly collagen. Injectable biostimulators, such as calcium hydroxyapatite (CaHA), represent a vital non-surgical strategy to counteract these changes by inducing neocollagenesis. This 90-day clinical trial was designed to comparatively evaluate the efficacy of a novel regenerative solution (RS) diluent, formulated to potentially enhance the biostimulatory effects of standard CaHA (STIIM product), against a conventional diluent (control) for the treatment of facial laxity. Twenty-one subjects (N = 21) were randomized to receive CaHA diluted with either RS or control formulation. Efficacy was assessed using histological analysis (collagen I area percentage), ultrasound (US) for dermal density, and clinical laxity scoring. Histological analysis, although limited by a small subsample size (N = 3), showed qualitative and exploratory evidence of collagen remodeling in both groups. However, the RS group showed enhanced dermal thickening via US (15% increase vs. 5% control, p-value = 0.012), and improvement in clinical laxity. Furthermore, histological findings, including Picrosirius red staining, indicated that the RS group resulted in qualitatively greater ECM organization and more robust type I collagen fibers compared to the control. The novel regenerative solution is safe and demonstrates enhanced neocollagenesis and clinical efficacy over the conventional formulation, validating its potential as a diluent for CaHA for optimized facial rejuvenation.

Background/Objectives: Calcium hydroxyapatite (CaHA)-based injectable materials are widely used as dermal biostimulators. In vitro models allow for controlled comparison of cellular responses and particle characteristics across formulations. This study aimed to compare two commercially available CaHA-based materials in terms of fibroblast metabolic activity, extracellular matrix-related gene expression, and microsphere morphology. Methods: Primary human dermal fibroblasts were exposed to two CaHA-based materials (Sample R and Sample S) at 10 mg/mL. Metabolic activity was assessed using the MTT assay at 24, 36, 48, and 72 h. Type I collagen and elastin gene expression were evaluated by RT-qPCR at 72 h. Microsphere morphology was analyzed by scanning electron microscopy (SEM). Results: Both materials increased fibroblast metabolic activity compared with the control at all time points. Early responses were similar, whereas Sample S showed higher activity at 48 and 72 h. At 72 h, both materials increased collagen and elastin gene expression versus the control, with greater responses observed for Sample S. SEM analysis showed predominantly spherical microspheres in both materials, with qualitative differences in surface microtopography. Conclusions: Under controlled in vitro conditions, both CaHA-based materials were biocompatible and modulated fibroblast metabolic activity and extracellular matrix-related gene expression. Differences in particle surface characteristics may contribute to the observed biological profiles. These findings support further studies incorporating extended incubation periods and protein-level analyses.

Background/Objectives: Depletion of nicotinamide adenine dinucleotide (NAD⁺) impairs dermal fibroblast function and accelerates skin aging. NAD⁺ precursors such as nicotinamide mononucleotide (NMN) and the reduced form, NADH, are therefore candidate cosmetic actives, but their comparative and combined effects in skin cells remain poorly explored. This in vitro study compared NMN alone, NADH alone, and an NMN + NADH co-formulation. Methods: Human dermal fibroblasts (HDFs) and human mesenchymal stromal cells (hMSCs) were treated with 10 mg/mL of NMN, NADH, or NMN + NADH. Expression of FOXO3, SIRT1, and SIRT3 (HDFs) and NRF2, NOG, and WNT5A (hMSCs) was measured by RT-qPCR, and cellular senescence was quantified by β-galactosidase staining. Results: All treatments increased gene expression relative to untreated controls (p < 0.05), except WNT5A in NMN-treated hMSCs. Increases ranged from 15.4% to 52.3% with NMN, 22.3% to 60.7% with NADH, and 30.5% to 78.1% with NMN + NADH. The co-formulation produced the highest mean expression in every panel and was significantly higher than both single compounds for FOXO3, NRF2, NOG, and WNT5A and higher than NMN for SIRT1; NADH exceeded NMN for NRF2 and WNT5A. The proportion of β-galactosidase-positive HDFs fell from 15.6% in controls to 4.8% (NMN), 3.4% (NADH), and 3.0% (NMN + NADH) (p < 0.01), with no significant differences among treatments. Conclusions: NMN, NADH, and their co-formulation each reduced senescence and modulated longevity-, antioxidant-, and tissue-homeostasis-related genes, with the co-formulation showing the largest transcriptional effects. Because the amount of each active differed between the single compounds and the co-formulation, additive, synergistic, and dose-related effects cannot be distinguished.

Background/Objectives: Cervical integument aging is a complex, multifactorial process characterized by thinning dermis, loss of elasticity, and platysmal band prominence. Multimodal treatments targeting these distinct anatomical layers simultaneously remain limited. This study aimed to evaluate the clinical efficacy, safety, and rejuvenation potential of the STIIM UP Protocol, a single-session treatment combining calcium hydroxyapatite (CaHA), hyaluronic acid (HA), and botulinum toxin type A (BoNT-A) for neck rejuvenation. Methods: This prospective, open-label, exploratory clinical study enrolled 13 healthy women (n = 13) presenting with cervical laxity. The STIIM UP suspension was delivered bilaterally into the subdermal plane of the anterior neck region using a retro-injection fanning technique with a 22G cannula at Day 0 (D0). Evaluated outcomes included the IBSA Neck Grading Scale, Global Aesthetic Improvement Scale (GAIS), FACE-Q module scores, and high-frequency ultrasound (USG) tissue thickness measurements at baseline and Day 120 (D120). Safety was monitored throughout. Results: The median consensus IBSA scores decreased significantly from 4.0 at baseline to 2.0 at both D30 and D120 (p-value < 0.01), indicating a rapid and sustained reduction in laxity. At D120, the GAIS responder rate reached 100% according to independent evaluators and 90.9% based on patient self-assessments. Quantitative USG confirmed statistically significant bilateral tissue thickening across the epidermis, dermis, and subcutaneous strata (p-value < 0.05). Progressive, clinically meaningful improvements were captured via the FACE-Q scales. No local or systemic adverse events were observed. Conclusions: The STIIM UP Protocol is a safe and effective multilayer intervention that successfully achieves comprehensive neck rejuvenation, bridging immediate clinical enhancement with sustained, tissue-proven structural remodeling.