Search Results (235)

Platelet-rich plasma (PRP) is widely utilized for skin rejuvenation and tissue regeneration; however, its biological effects vary according to leukocyte content and molecular composition. We investigated the mechanism by which leukocyte-rich PRP (L-PRP) enhances extracellular matrix (ECM) regeneration in aged skin, focusing on the CCL1-CCR8/pyruvate kinase M2 (PKM2) signaling axis. First, we demonstrated that L-PRP contains significantly higher levels of CCL1 than platelet-poor plasma (PPP). In senescent human dermal fibroblasts, L-PRP increased CCL1-CCR8 interactions in a manner linked to enhanced formation and nuclear translocation of PKM2 dimers. This enhancement was accompanied by Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway activation and the upregulation of STAT3-dependent anti-apoptotic proteins (Bcl-2, Bcl-xL) and proliferative markers (Cyclin D1), resulting in increased fibroblast proliferation. Furthermore, L-PRP increased PKM2 tetramer levels, promoted PKM2-SMAD7 binding, and reduced SMAD7-mediated inhibition of transforming growth factor (TGF)-β signaling, leading to enhanced SMAD2/3 activation. These molecular events augmented the synthesis of collagen types I and III in senescent fibroblasts. In aged mice, intradermal L-PRP injections elicited dose-dependent increases in fibroblast proliferation, collagen fiber deposition, and skin elasticity. Nuclear PKM2 dimer/STAT3 signaling and PKM2 tetramer/TGF-β signaling were both more strongly activated in the L-PRP group. Our findings identify PKM2 as a central metabolic and signaling integrator linking immune-derived chemokines to fibroblast rejuvenation. This study provides mechanistic insights concerning how L-PRP promotes ECM regeneration in aged skin via coordinated regulation of fibroblast survival, proliferation, and collagen synthesis. Full article

Skin aging is associated with collagen degradation, wrinkle formation, enlarged pores, pigmentation changes, and reduced overall skin quality. This pilot comparative clinical study evaluated the short-term effects of HIFU monotherapy, microneedling-assisted EXO-PDRN therapy, and sequential HIFU followed by microneedling-assisted EXO-PDRN using AI-assisted digital skin analysis. Twenty-eight healthy adults aged 45–55 years were allocated into four groups: control, HIFU, MN–EXO-PDRN, and HIFU + MN–EXO-PDRN. Each active monotherapy group received one treatment session, while the combined group received one HIFU session followed seven days later by one microneedling-assisted EXO-PDRN session. Final follow-up assessment was performed at 30–40 days, according to the intervention timeline of each group. The primary descriptive outcome was the median percentage change from baseline. HIFU produced the greatest median reductions in wrinkles (−48.6%) and pores (−49.4%), whereas HIFU + MN–EXO-PDRN demonstrated broader early improvements in sensitivity (−55.9%), wrinkles (−39.3%), pores (−33.3%), UV spots (−19.1%), and global pixel-based skin burden (−29.9%). Control-group increases were interpreted cautiously due to the exploratory design and potential measurement variability. Larger randomized studies with longer follow-up are warranted. Full article

Background: Cutaneous microcirculation is crucial for skin appearance and rejuvenation, influencing color, luminosity and texture. Aging reduces microcirculation and alters skin color parameters. This study investigated the long-term effects of intradermal CellBooster^® Lift (CBL), a mechanically stabilized hyaluronic acid complex enriched with amino acids and vitamins, on skin microcirculation, color, and aesthetics in healthy adults. This study was registered at clinicaltrial.gov (NCT06000839). Methods: 36 women and 4 men aged 35–55 received three intradermal injections of 3 mL CBL across the face at two-week intervals. Cutaneous microcirculation was assessed using a PeriFlux 5000^® laser Doppler system at 7 and 84 days post-treatment. Skin color parameters, including lightness (L*), redness (a*), yellow-blue component (b*), individual typology angle (ITA°), individual whitening angle (IWA°), color homogeneity (H76), saturation, and luminance-saturation ratio, were analyzed using Visia^® CR 2D imaging. Aesthetic improvement was evaluated by both participants and medical practitioners using the Global Aesthetic Improvement Scale (GAIS). Results: At 84 days post-treatment, CBL significantly enhanced cutaneous microcirculation and induced favorable changes in all measured skin color parameters: L*, ITA°, IWA°, and luminance-saturation ratio increased, while a*, b*, H76, and saturation decreased in women, but no changes were seen in men. No significant differences were observed between female age groups. On the GAIS, approximately 70–73% of participants reported improvement or significant improvement, while medical practitioners rated improvement in up to 93% of cases. Conclusions: Intradermal CBL administration improves cutaneous microcirculation and skin color characteristics, contributing to a more youthful appearance in adults aged 35–55, with consistent effects across age groups and high subjective and clinical aesthetic ratings. Full article

This study aimed to evaluate whether the Synerjet system can maximize the transdermal delivery and skin rejuvenation of nano-NMN. In a 4-week split-face trial (n = 21), this combination demonstrated marked clinical superiority over topical nano-NMN alone (p < 0.001), yielding enhanced improvements in wrinkles (with 170.56% relative improvement in periorbital and 154.45% in nasolabial region compared to the control group), pore volume (176.62%), and deep hydration (188.02%). Regarding dermal integrity, the test group showed a 111.56% superior increment in skin elasticity and a 149.75% more effective optimization of melanin intensity relative to the control. Notably, deep-tissue hydration at a 2.5 mm depth demonstrated a 188.02% higher gain, suggesting that the modality significantly fortifies the skin’s physiological moisture reservoir. The test group exhibited a marked improvement over the control across all cutaneous parameters (p < 0.001). Our findings demonstrate that a new combinatorial approach using EP-assisted microjet of a Synerjet system after cold plasma pretreatment and a nano-NMN 10% ampoule resulted in significantly greater improvements in wrinkles, pores, elasticity, pigmentation, and deep skin hydration compared to topical application alone. Consequently, these results demonstrated that the Synerjet system effectively overcame the inherent limitations of nano-delivery technologies, offering a promising modality for advanced cutaneous rejuvenation and a robust framework for future professional dermatological treatments. Full article

The periorbital region represents one of the most challenging anatomical sites in aesthetic medicine due to its thin dermis, complex vascularity, and susceptibility to oedema and contour irregularities. While hyaluronic acid (HA) fillers remain the gold standard for volumetric correction, their limitations in skin quality enhancement and risk of complications such as Tyndall effect and malar oedema have driven interest in regenerative alternatives. Polynucleotides (PN), particularly polydeoxyribonucleotides (PDRN), have emerged as bioactive agents capable of promoting dermal remodelling, angiogenesis, and anti-inflammatory responses. This review critically evaluates current evidence comparing PN and HA in periorbital rejuvenation, integrating mechanistic insights, clinical outcomes, and safety considerations. While HA remains superior for structural correction, PN demonstrates consistent improvements in dermal quality parameters, including elasticity, hydration, and fine rhytids, with a favourable safety profile. However, heterogeneity in study design, product formulation, and outcome measures limits the ability to draw definitive conclusions. Future research should prioritise standardised protocols, long-term follow-up, and direct comparative trials to establish optimal treatment algorithms. Full article

Extracellular vesicles (EVs), particularly small extracellular vesicles (sEVs), are lipid bilayer-delimited particles involved in intercellular communication through the transfer of proteins, lipids, and nucleic acids; many products and studies in aesthetic medicine refer to these preparations as exosomes, although endosomal origin is not always demonstrated. This review examines current evidence on the mechanisms, clinical effectiveness, safety, therapeutic applications, and regulatory challenges of EV- and sEV-based interventions, complemented by an exploratory qualitative assessment of physicians’ perceptions regarding clinical implementation. A narrative review of studies indexed in Scopus and PubMed was conducted with emphasis on skin rejuvenation, hair restoration, wound healing, pigmentation disorders, and inflammatory dermatoses, and responses from 12 aesthetic physicians in Colombia were analyzed qualitatively. Available evidence suggests that EVs/sEVs may promote extracellular matrix remodeling, angiogenesis, immunomodulation, and tissue repair, with potential benefits across several aesthetic and regenerative indications. However, the literature remains heterogeneous and limited by variability in biologic sources, isolation and administration protocols, insufficient high-quality clinical trials, and unresolved regulatory issues. Reports of adverse reactions linked to unapproved products marketed as exosome-based formulations further highlight the need for stronger oversight. EVs, particularly sEVs, often referred to as exosomes in the aesthetic literature, remain a promising therapeutic platform, but safe clinical integration requires rigorous validation, technical standardization, and robust regulatory frameworks. Full article

In 1988, plastic surgeon Lee Dellon in Annals of Plastic Surgery hypothesized that there was “A Cause for Optimism in Diabetic Neuropathy”. He noted that entrapment neuropathy is common in diabetic peripheral neuropathy (DPN) and explained that multiple sites of local nerve entrapment can also produce the classically described clinical picture of progressive and irreversible ‘length dependent axonopathy’. This observation has justified for him the use of nerve decompression (ND) surgery for beneficial treatment of DPN pain, diabetic foot ulcer (DFU), ulcer recurrences and their subsequent complications. Subsequent observational and controlled reports have consistently demonstrated post-operative benefit for these problems, but ND has not yet been widely adopted. The lack of an etiologic explanation of the physiology changes which would allow surgery to modify the metabolic disturbances of diabetes has likely been involved in such hesitance. Recent explanations that glycolysis is altered in diabetes through intensified polyol metabolism which produces swollen nerves, local peripheral entrapments and compression neuropathy now provide plausible associations of hyperglycemia with epidermal hypoxia and nutrition deficit. Recognition that nerve enlargements can create secondary fibro-osseous compressions explains the well-known association of diabetes and compression syndromes. Peripheral nerve entrapments damage small c-fibers and produce sympathetic autonomic as well as sensorimotor dysfunction. This explains the diminished skin microcirculation, epidermal hypoxia and nutrition deficit seen in diabetes, DPN, DFU and Charcot neuroarthropathy. Laboratory and clinical evidence has demonstrated that ND in diabetes rejuvenates at least two sympathetically commanded skin microcirculation processes and explains how surgery is producing beneficial results. This article recapitulates the literature which clarifies the processes by which ND surgery can modify painful DPN, DFU occurrence, ulcer healing, DFU recurrence risk, amputations after DFU healing, and bilateral pain relief after unilateral surgery. Full article

Monopolar radiofrequency (MRF) is a well-established modality for non-invasive facial rejuvenation; however, its clinical utility is frequently constrained by patient discomfort and inconsistent thermal delivery. This study evaluated the efficacy, safety, and mechanistic profile of a novel MRF system incorporating continuous water cooling (RF-CWC) designed to optimize thermal distribution and enhance patient tolerance. In a prospective, single-arm clinical trial involving 22 female participants, a single RF-CWC treatment utilizing region-specific static and sliding delivery modes yielded statistically significant improvements in jawline lifting, alongside a volumetric increase in the midface and a concomitant volumetric reduction in the lower face (p < 0.001) over an 8-week follow-up period, with no adverse events reported. To elucidate the underlying cellular mechanisms, the system was further evaluated using an ultraviolet B (UVB)-induced ex vivo human skin model and an in vivo porcine model. Histological, immunohistochemical, and ELISA analyses revealed that RF-CWC effectively mitigated UVB-induced dermal degradation ex vivo by significantly up-regulating elastin, insulin-like growth factor, and hyaluronic acid, while down-regulating matrix metalloproteinase-1, interleukin-1α, and heat shock protein 72 (p < 0.05). Furthermore, the in vivo model demonstrated time-dependent increases in collagen types I and III and elastin without thermal tissue damage, with the sliding mode and higher shot counts correlating with enhanced extracellular matrix (ECM) remodeling. Comparative analyses demonstrated that RF-CWC achieved superior ECM restoration and reduced inflammatory cell infiltration relative to traditional cryogen spray-cooled RF systems. Taken together, these findings suggest that the RF-CWC system may promote robust ECM remodeling and significant facial neocollagenesis while minimizing inflammatory responses, potentially presenting an optimized, highly effective, and patient-friendly advancement in MRF technology. Full article

Skin aging stems from intrinsic decline and external stressors that induce oxidative stress and mitochondrial damage, ultimately lowering cellular energy production and slowing epidermal turnover to cause wrinkles, dryness, and pigment imbalances. While disodium adenosine monophosphate (AMP2Na) is hypothesized to enhance cellular adenosine triphosphate production and restore epidermal metabolism, its broader anti-aging effects have remained underexplored. To address this, a multi-tiered study integrating in vitro, ex vivo, and clinical investigations was conducted. Specifically, a 12-week exploratory clinical trial involving female participants with facial hyperpigmentation (n = 23), alongside a short-term forearm study (n = 22), suggested that the AMP2Na-containing product could reduce wrinkles and hyperpigmentation while safely improving hydration, barrier function, skin lifting, and epidermal turnover with high participant satisfaction. Mechanistically, in vitro assays on human dermal fibroblasts showed that the formulation restored antioxidant enzyme activity and mitigated senescence. Ex vivo UVB-irradiated skin explant models corroborated these findings by revealing reduced melanin levels, preserved collagen and elastin networks, and an upregulation of key structural and barrier-related proteins. Ultimately, by potentially supporting epidermal turnover and restoring barrier function through this biomimetic mechanism, the AMP2Na-containing product might offer a promising option for alleviating wrinkles, dryness, and hyperpigmentation. Future randomized, vehicle-controlled clinical trials and comprehensive laboratory studies are warranted to validate its true potential in skin rejuvenation. Full article

Background: Retinol has consistently demonstrated efficacy in improving signs of skin aging. However, recent European Union regulations have limited its cosmetic concentration to 0.3%, creating the need for new formulations to be capable of maintaining high efficacy, safety, and tolerance. Material and Methods: This clinical study aimed to evaluate and compare the rejuvenating effects and tolerance of a 0.5% retinol serum with a new equivalent technology, Retinduo^®, which previously showed promising preclinical results. A single-center, prospective, randomized, controlled, double-blind, two-arm parallel study was conducted in 40 Caucasian women aged 38–60 years with moderate photoaging (Glogau II). A total of 20 participants applied Retinduo^® serum and 20 applied retinol 0.5%, following a progressive application protocol. Clinical and instrumental assessments measured hydration, firmness, elasticity, tone homogeneity, melanin levels, skin roughness, wrinkle parameters, and stratum corneum thickness. Results and Discussion: Both formulations significantly improved hydration, firmness, and elasticity from day 28 onward. Retinduo^® showed a significant increase in viscoelasticity (R8) from day 56, while retinol 0.5% did not demonstrate significant changes in this parameter. Melanin reduction was observed with Retinduo^® at days 28 and 56 and with retinol 0.5% just at day 28. Although a reduction in melanin was observed with both ingredients, the reduction was more significant with Retinduo^® at 56 days. Both treatments reduced the thickness of the stratum corneum; however, with Retinduo^®, a significant and more pronounced reduction was achieved after 3 months of treatment (30% (p = 0.0001) vs. 12% (p = 0.033). Retinduo^® demonstrated significant wrinkle depth reduction at day 28 and in wrinkle amplitude (width and length of wrinkles) at the end of treatment, while 0.5% retinol showed a positive trend in this parameter. Both products exhibited excellent tolerance. Conclusions: Overall, Retinduo^® achieved comparable or slightly superior anti-aging effects while aligning with current European regulatory limits. Full article

The integration of exosomes into professional cosmetics marks a significant paradigm shift from traditional passive formulations to advanced regenerative esthetics. Rather than being defined solely by their nanometric dimensions or classical association with endosomal biogenesis, these vesicles function as highly targeted intercellular messengers capable of delivering complex bioactive payloads to modulate tissue repair and collagen synthesis. While robust preclinical and clinical trials validate their remarkable potential in skin rejuvenation, hair restoration, and hyperpigmentation management, significant translational barriers remain. A critical analysis of the current literature reveals that successful clinical outcomes frequently rely on physical penetration enhancers, such as microneedling or fractional lasers, making it challenging to isolate the autonomous efficacy of topical vesicles from the trauma-induced regenerative response. Furthermore, commercial viability is dictated by stringent regulatory frameworks. In the European Union, Regulation (EC) No 1223/2009 strictly prohibits human-derived biologicals, while the US Food and Drug Administration (FDA) aggressively monitors the unsubstantiated marketing of cellular therapies. To navigate these biosafety and legal constraints, the aesthetic industry is increasingly pivoting toward non-human and legally compliant alternatives. Consequently, Plant-Derived Extracellular Vesicles (PDEVs), microbiome-derived exosomes (such as those obtained from bacterial fermentation), and bioengineered synthetic analogues have become the focal point of market innovation. A practical evaluation of the MCCM Medical Cosmetics portfolio illustrates this strategic shift, demonstrating the clinical versatility of botanical sources. To secure the long-term credibility of exosome technology, the industry must overcome current manufacturing heterogeneity by aligning with international standardization frameworks, such as the MISEV2023 guidelines, thereby ensuring reliable delivery systems, batch-to-batch consistency, and uncompromised consumer safety. This review provides a comprehensive overview of the biological mechanisms, clinical efficacy, and translational challenges associated with exosome-based cosmetics. Full article

Aesthetic medicine is shifting from symptomatic correction to biological structural restoration. Regenerative aesthetics represents a frontier in dermatology, focusing on the restoration of the skin microenvironment to enhance cellular vitality and tissue resilience. Central to this approach is the concept of “skin bed preparation”, a strategic priming phase designed to optimize the physiological terrain before the delivery of advanced aesthetic interventions. This review explores the molecular and cellular mechanisms by which skin bed preparation modulates the extracellular matrix (ECM) and the dermal niche to maximize the efficacy of subsequent treatments and promote long-term skin longevity. Evidence suggests that biostimulatory priming utilizing senolytics, senomorphics, mitochondrial, and/or epigenetic rejuvenators rehabilitates the fibroblast–collagen interactome. By reducing oxidative stress and chronic low-grade inflammation, these preparatory steps transition the skin from a catabolic to an anabolic state. This metabolic reset ensures that subsequent procedures, such as laser therapy, injectable fillers, encounter a responsive cellular environment, resulting in superior collagen induction and prolonged clinical outcomes. Optimizing the skin microenvironment via regenerative aesthetics is not merely an adjunctive step but a fundamental requirement for therapeutic success. Integrating skin bed preparation into clinical protocols provides a synergistic framework that enhances immediate procedural results while addressing the underlying hallmarks of skin aging, ultimately redefining the trajectory of skin health and longevity. Full article

This study evaluated the safety and effectiveness of HYDRAGEL A2, an injectable medical device containing hyaluronic acid (HA), polynucleotides (PN), and niacinamide, for improving facial skin quality. These ingredients are increasingly recognized for their synergistic effects in aesthetic medicine, with HA and PN providing hydration and skin support, and niacinamide offering anti-inflammatory and antioxidant properties. A prospective, open-label clinical investigation was conducted on 42 female subjects (mean age 45 ± 1 years, Fitzpatrick skin phototypes II-V) to assess skin elasticity, hydration, and mild skin depression correction following cheek area injections. Efficacy was measured using the Global Aesthetic Improvement Scale (GAIS), Antera 3D^® (texture), Cutometer^® (elasticity/firmness), Corneometer^® (hydration), and Dermascan^® (density/thickness) devices at baseline (D0), week 2 (W2/D14), and week 6 (W6/D42). GAIS values showed significant overall facial improvement (p < 0.001) by both investigators and subjects, where 100% of subjects rated their appearance as improved immediately post-injection (D0), with sustained improvements at D42. Objective measurements revealed significant improvements in skin texture (reduced roughness), elasticity, firmness, hydration (p < 0.001), density, and thickness, demonstrating the combined benefits of the HA, PN, and niacinamide blend. Injection site reactions, primarily mild and transient, were reported immediately post-injection. Investigators and subjects reported high satisfaction with the product’s ease of use and aesthetic outcomes. Globally, HYDRAGEL A2, leveraging the established benefits of HA, PN, and niacinamide, was well-tolerated and effectively enhanced facial skin quality, demonstrating significant and sustained improvements in monitored skin parameters. The study concludes that this combination of ingredients, formulated in HYDRAGEL A2, provides a well-tolerated approach associated with improvements in skin quality. Full article

Exosomes are revolutionizing skincare as natural messengers for cell communication, yet their transition into cosmetics is often limited by the ethical and regulatory hurdles of their animal or human sourcing. This study describes the development and validation of vegan exosome-like biomimetic vesicles (EBVs) generated from the microalgae Chlamydomonas reinhardtii that reproduce the structural and functional logic of mammalian exosomes. Their structural biomimetism was confirmed through physical, lipidomic, and proteomic characterizations, revealing bilamellar vesicles (average diameter ~160 nm) containing 109 membrane lipids and 1369 proteins. Their functional biomimetism was assessed via 3′ mRNA sequencing, which showed that the EBVs induced transcriptional responses in human fibroblasts functionally analogous to human-derived exosomes in matrix-remodeling and anti-aging pathways. In vitro, the EBVs showed a 166.7% higher dermal delivery bias than standard liposomes and accelerated wound healing. Ex vivo, 2% EBVs protected skin explants against UV-A stress, showing 92% protective efficacy for excessive melanin production upon oxidative stress. Furthermore, the EBVs supported hair follicle anagen markers and follicle stem cell metabolism, significantly upregulating SOX9 (p = 0.0022). A 56-day placebo-controlled clinical study confirmed significant improvements in wrinkle depth (−12.2%), elasticity (+4.9%), and radiance (+20.0%). These results position EBVs as a scalable, high-performance alternative for next-generation anti-aging cosmetic applications. Full article