Background Solar elastosis (SE) is the end result of long-term sun damage, characterized by a buildup of dystrophic material in the extracellular matrix (ECM) surrounded by fragmented collagen and dysfunctional, aggregated elastin. This degenerative process was once thought to be irreversible but is now recognized as dynamic, with the potential for regenerative change through appropriate interventions. New stains also enable the detection of newly formed elastin and collagen as part of this reversal process.Materials and Methods A retrospective analysis of multiple clinical studies (624 patients, 80 biopsies, 31 reported solar elastosis) was conducted, focusing on the use of TriHex and TriHex+ peptide-based technology (Alastin Skincare Inc., Carlsbad, CA). Biopsies were evaluated using novel histologic stains, including Herovici and Movat, alongside conventional Hematoxylin & Eosin (H&E) and CD44. Markers such as Collagen IV and Laminin at the dermo-epidermal junction (DEJ) were also assessed to identify evidence of regenerative reversal of solar elastosis, ECM remodeling, and new elastin formation.Results The regenerative reversal of solar elastosis was observed across multiple clinical trials. The TriHex formulations consistently produced significant improvements in ECM structure. Reported histology in 74% of cases showed clear removal of amorphous elastotic deposits and restoration of the ECM, including new elastin fiber formation, strengthening of the DEJ with increased Collagen IV and Laminin, new rete ridge architecture, and positive hydration effects evidenced by increased CD44 staining.Conclusion This review positively challenges a long-standing myth and clearly establishes a new perspective: solar elastosis is reversible. The peptide-based TriHex Technology can remove the elastotic amorphous material from the ECM and rebuild it with new elastin and collagen fibers. Clinically and histologically, this shows that chronic sun damage can be repaired in the dermis, supporting a shift from superficial treatments to a more targeted regenerative approach focused on restoring the structural integrity of the skin.

BACKGROUND:Skin thinning, known as dermatoporosis, is an expected consequence of aging that involves structural weaknesses, barrier deficiencies, and cellular senescence, posing challenges for maintaining long-term skin health. OBJECTIVE:To introduce Skin Activation as a dermatologic strategy for promoting skin longevity. It is supported by clinical and preclinical evidence, combining methods to remodel the extracellular matrix (ECM) and dermo-epidermal junction (DEJ), restore the barrier, and enhance hydration, along with reducing senescent cells. This improves the skin's functional resilience. METHODS:Data were generated from a multicenter dermatoporosis trial, a randomized controlled trial, and specific cohorts of sensitive skin patients, in addition to preclinical studies. Study endpoints included trans-epidermal water loss (TEWL), hydration levels, LC-Optical Coherence Tomography (LC-OCT), assessments of the DEJ, ultrasound measurements, senescent markers, and histology. The data also included measures of senescence, cytokine profiles, and biomarkers of cellular renewal. RESULTS:Among 400 participants, notable changes included a 20-40% reduction in TEWL, an 80% increase in hydration based on corneometer readings, a 5% rise in skin thickness, and improved DEJ integrity in 83% of subjects compared to 17% of controls. In preclinical ex vivo models, decreases in fibroblast senescence levels were observed, along with activation of the JAG/NOTCH pathway. CONCLUSION:A recently developed skin activator program shifts dermatologic skin health strategies from a broad anti-aging focus to a more targeted skin activation approach focused on structure, function, and cellular energy and renewal. This reinforces the ongoing commitment to dermatological innovation and establishes a more structured approach to skin longevity. &nbsp.

BACKGROUND:Dermatoporosis (DP) or chronic cutaneous fragility syndrome has traditionally been linked to extracellular matrix (ECM) dehydration, reduced cellular turnover, epidermal thinning, and vascular fragility. However, recent imaging methods and clinical evidence indicate that the dermoepidermal junction (DEJ) might be the earliest change reflecting DP reversal. OBJECTIVE:To propose a new mechanistic process in which the DEJ acts as the initiation point for reversing the DP. The process is supported by clinical and imaging evidence, as well as independent literature on DEJ biology. METHODS:A combination of clinical and investigational findings, published theoretical models, and evidence from wound-healing, skin-longevity reports, ex vivo model analyses, and device-based interventions formed the basis for the scientific narrative. RESULTS:Cumulative evidence suggests that an initial change in the DEJ, along with structural restoration, appears to trigger or initiate regenerative processes in the ECM and epidermis. These include the renewal of basal stem cells following adhesion signaling in the basement membrane; ECM remodeling through improved communication between the dermis and epidermis, along with enhanced fibroblast interactions involving collagen and elastin; and finally, ECM remodeling and stabilization of basement membrane anchoring provides support and stability to blood vessels, protecting them from recurrent injury. CONCLUSION:The DEJ acts as a bridge between the epidermis and dermis, providing structural support while also triggering signaling cascades that promote a regenerative environment, contributing to DEJ reversal. Targeting the DEJ could be a logical therapeutic approach, establishing a new paradigm for biomarker analysis and an intervention site for regenerative initiation. &nbsp.

Background: Injectable biostimulator treatments stimulate endogenous collagen in aging skin, but whether they act through similar pathways is unknown. This study evaluates two biostimulatory agents' effects on genes, expressed proteins, and respective pathways as potential aging biomarkers and treatment outcomes. Methods: This 13-week, randomized, single-center, comparative study compared volume change and gene expression stimulated by poly-L-lactic acid (PLLA-SCATM) and calcium hydroxylapatite (CaHA-R) via punch biopsy in the nasolabial fold (NLF). Subjects (n=21) had shallow NLF contour deficiencies on the wrinkle assessment scale (WAS) >= 2 and identical WAS scores on both sides of the nose. Biopsies at baseline and 90 days were analyzed for gene expression of targeted biomarkers. These results were assessed using the STRING and Reactome databases to determine functional pathways, as well as gene markers and their respective pathways. Results: Gene analysis suggested unique processes for each biostimulator. PLLA-SCA stimulated more components of the extracellular matrix with less inflammatory response, translating to a more regenerative pathway. CaHA-R elicited a more inflammatory response that could diminish tissue regeneration, translating to a pro-inflammatory pathway. Conclusions: PLLA-SCA is associated with regenerative pathways, while CaHA-R did not show evidence of tissue regeneration and upregulated more genes in pro-inflammatory pathways. J Drugs Dermatol. 2025;24(1):34-40. doi:10.36849/JDD.8464R1.

Dipeptidyl-peptidase 4 inhibitors, DPP-4i, are an established antiglycaemic medication for Type 2 Diabetes. There has been a growing interest in DPP-4i's potential to improve wound healing and reduce fibrosis. The purpose of this study is to survey the current literature for applications of DPP-4i in wound healing and scars, and explore their potential outside of glycaemic control. A systematic review was performed by three independent reviewers according to PRISMA guidelines using PubMed, SCOPUS, Embase and Cochrane CENTRAL databases. Search terms were synonymous with 'DPP-4i', 'diabetic wounds', 'wound healing', 'scars' and 'skin'. Studies that used DPP-4i in the context of wound healing, scarring, or psoriasis were included for data extraction. A total of 2139 articles were screened, resulting in 31 human, animal and in vitro studies. Human studies showed DPP-4i led to faster wound closure rates, clinical improvement in psoriasis and a reduced risk of keloid formation after sternotomy. In vitro studies reported an increase in cell migration, proliferation and angiogenesis with DPP-4 inhibition. DPP-4i was found to attenuate markers of fibrosis in multiple wound healing models and downregulate TGF-β, pSmad2/3, α-SMA, Col1, Col3 and downstream effectors of the MAPK-NF-κB pathway. This systematic review is the first to summarise and shed light on DPP-4i therapeutic benefits for wound healing and scarring. In multiple in vitro, animal and human studies, DPP-4i have a net positive effect on cutaneous healing. Further studies are needed to reveal the specific molecular pathways through which DPP-4 exerts its effects, particularly in relation to wound healing, scar formation and angiogenesis.

BackgroundAlastin Restorative Skin Complex Serum with TriHex Technology (Alastin Skincare Inc., Carlsbad, CA) has undergone reformulation to add Octapeptide-45 and magnolol for improving facial skin hydration, elasticity, plumping, and overall skin quality. Detailed science on TriHex Technology 2.0 and magnolol has been recently published. This open-label study was conducted to validate the science and demonstrate product efficacy and tolerability in individuals with moderate to severe facial skin aging.MethodsA multi-center clinical study was conducted from February to August 2024. A total of 44 eligible participants (43 female, 1 male), ages 35-69 years, and Fitzpatrick skin Types I-VI were enrolled in and completed the study following 12 weeks of Alastin Restorative Skin Complex Serum 2.0 with TriHex Technology (RSC 2.0) use twice daily, along with an Alastin Skincare Inc. supportive regimen (cleanser, moisturizer, sunscreen used as needed). A 1-week run-in phase using the supportive regimen only was conducted, and eligibility was reassessed at baseline. Follow-up visits were performed at Weeks 4, 8, and 12, where facial skin quality parameters were evaluated clinically and subject assessments and satisfaction questionnaires, biopsy collection, photography, and hydration and elasticity measurements were completed. Participants also maintained a study diary over the 12-week treatment period.ResultsSignificant improvements for all clinically evaluated facial skin parameters were achieved at Week 12. Histology revealed increased stimulation of new adipocytes, epidermal keratinocyte HA (CD44), and new dermal collagen and elastin fibers post treatment.ConclusionAlastin Restorative Skin Complex Serum 2.0 with TriHex Technology has been demonstrated to be safe and effective for improving overall facial skin quality, achieving notable improvements in volume, plumping, hydration, and extracellular matrix (ECM) collagen and elastin stimulation.

BACKGROUND:The clinical presentation of photodamaged and aged skin includes fine lines, wrinkles, and pigmentation changes, which are related to the amount of water in the epidermis. Use of moisturizing products can help improve signs of aging. METHODS:Twelve (12) week single-center study in participants 40 to 75 years old with sensitive skin and signs/symptoms of photodamage and skin aging (defined as mild-to-moderate wrinkles, overall photodamage, and lack of skin tone evenness on the neck and outer forearms). Participants applied a cream twice per day to the body (neck, legs, arms, and hands). Efficacy was assessed by clinical grading and digital imaging (in a subgroup of 19 participants) and standard safety assessments were performed. RESULTS:A total of 41 participants participated. All clinical grading parameters showed significant improvements, including crepiness (visual), skin texture/smoothness (tactile), and overall quality/appearance. In addition, density/thickness improved on both neck and limbs throughout the study. Pinch recoil measurements also improved from baseline to day 84. Tolerability assessments showed improvement of dryness and scaling on limbs vs baseline and no measurable change in any other tolerability parameters throughout the study. In addition, participants reported a positive impression of the cream on a self-assessment questionnaire. CONCLUSIONS:The tested cream, which incorporates the ingredients mandelic acid and Centella asiatica, effectively improved participants' skin appearance in adults with sensitive skin and moderate signs of aging. CITATION:Widgerow A, Grivet-Seyve M, Anjuwon S, et al. Efficacy and tolerability of a cream in aging skin. J Drugs Dermatol. 2025;24(5):524-529. doi:10.36849/JDD.9025.

Autologous fat grafting of human lipoaspirate (LA) is increasingly used in reconstructive and cosmetic surgery for lipofilling and stem cell-rich "nanofat" reinjection for regenerative medicine. While commercial devices (e.g., REVOLVE and Puregraft) are available, many surgeons use non-standardized manual washing techniques, leading to inconsistent graft retention (20-80%). Moreover, no system can unite washing directly with mechanical processing to produce a nanofat-like product directly from raw LA. We developed a novel preparation device (PD) that is designed for peristaltic pump-driven washing of LA and can be seamlessly combined with our previously developed Emulsification and Micronization Device (EMD) into an automated closed-loop platform. Human LA samples were washed with the PD and compared to standard manual washing via visual colorimetric analysis. We then evaluated the mechanical processing of PD-washed LA using our EMD and assessed cell count, viability, and stromal vascular fraction-derived subpopulations (i.e., mesenchymal stem cells, endothelial progenitor cells (EPCs), pericytes, transit-amplifying (TA) progenitor cells, and supra-adventitial adipose stromal cells). Recirculating LA through the PD for at least one minute resulted in sufficient mixing, producing LA with equivalent color and quality to manual washing. Integrating the EMD within a platform enabled both washing and mechanical processing under peristaltic flow, enriching key subpopulations compared to manual methods. Thus, our fluidic platform effectively washes LA in a closed-loop system, minimizing LA tissue manipulation and opportunity for contamination while also simplifying the workflow for mechanical processing. Further refinement and automation of this platform would enhance the reproducibility and quality of small-volume fat grafts, cell-assisted lipotransfer, and stem/progenitor cell injections to promote wound healing and angiogenesis.

PURPOSE:Transforming myofibroblasts (MFs) into adipocyte-like cells may be a viable option for treating Dupuytren disease. Human Dupuytren MFs (DMFs) and adipose-derived stem cells (ASCs) cocultured in the presence of platelet-rich plasma (PRP) reprogrammed into lipid-laden cells. This treatment also reduced fibrosis markers in vivo. We aimed to determine whether this treatment transformed DMFs into adipocyte-like cells in vivo and characterize the PRP factors contributing to this transformation. METHODS:Dupuytren MFs and normal human dermal fibroblasts were transplanted into the forepaws of rats (Rowett Nude [rnu/rnu]). Two months later, the paws were treated with saline, ASCs + PRP, or Clostridium histolyticum (clinical comparison) once a week for three treatments. The paw tissue was harvested 1 week after each treatment and subjected to Masson trichrome staining, collagen I and III, α-smooth muscle actin (SMA), and perilipin detection by immunohistochemistry. Dupuytren MFs were cocultured with ASCs and PRP or insulin-like growth factor I (IGF-I) or IGF-I-depleted PRP. In addition, the IGF-I receptor was inhibited. Oil Red O or boron-dipyrromethene detected lipid-laden cells. RESULTS:Rodent paws implanted with DMFs showed enhanced α-SMA expression, imbalanced collagen III:I ratio, and reduced adipocytes compared with normal human dermal fibroblasts. After treatment with ASCs + PRP, DMF paws demonstrated reduced α-SMA, a balanced collagen III:I ratio, and a replenishment of adipocytes. Dupuytren MFs treated with ASCs + IGF-I transformed into adipocyte-like cells in vitro, which was validated by IGF-I-depletion and IGF-I receptor inhibition. CONCLUSIONS:Adipose-derived stem cells + PRP reduce fibrosis markers and induce adipocyte renewal in vivo. As a PRP component, IGF-I works with ASCs to transform DMFs into adipocyte-like cells in vitro. CLINICAL RELEVANCE:Identifying an active factor in PRP that synergizes with ASCs to transform DMFs into adipocyte-like cells may contribute to finding a novel therapeutic for Dupuytren disease. Such a treatment may allow for less-extensive surgical intervention coupled with therapeutic injection to reduce the recurrence of Dupuytren disease.

BACKGROUND:Mechanical processing of lipoaspirate (LA) produces a stromal vascular fraction (SVF) without enzymatic digestion for use in aesthetic, surgical, and regenerative applications. We recently presented novel device technologies that increased mesenchymal stem cell (MSC) content relative to standard nanofat (NF) processing. OBJECTIVES:Here, we introduce a third technology designed to enhance fluid shear forces and explore the impact of mechanical processing on regenerative potential in vitro. METHODS:Human LA samples were processed with our previously reported emulsification micronization device and filtration device, and then optimized using a new shearing device (SD). Results were analyzed for total cell count, viability, and percentages of endothelial progenitor cells (EPCs) and MSCs compared to manual NF processing, both immediately and following 24-hour culture. Expression of genes related to wound healing was quantified by real-time quantitative polymerase chain reaction, and angiogenic capacity was determined with an in vitro 3-dimensional sprouting assay. RESULTS:The SD did not significantly affect MSC recovery or viability, but EPCs were enriched in a shear stress-dependent manner. Gene expression was not altered immediately after processing, but after culture we noted changes to wound-healing transcriptional programs that were consistently stronger for our devices than NF. Differences were statistically significant for CXCL1, IL1β, IL6, CSF3, and COL1A2. Notably, angiogenic vessel sprouting was significantly enhanced for our devices compared to NF. CONCLUSIONS:Mechanical processing of lipoaspirate with our 3-device platform resulted in greater enrichment of stem and progenitor cells, activation of genes implicated in wound healing, and induction of angiogenesis in vitro relative to NF. Future studies will ascertain potential implications in vivo for all indications that currently utilize NF, as well as automate the process within an integrated system.

BACKGROUND:There is increasing recognition of dermatoporosis - a condition of chronic cutaneous fragility of aging skin seen primarily in older adults. Dermatoporosis can be characterized by white pseudo scars, purpura/bruising, skin thinning, and loss of volume. This study evaluated a novel cream with microdoses of mandelic acid and Centella asiatica that was formulated to target physiologic processes involved in dermatoporosis. METHODS:A 12-week, proof-of-concept study of participants aged 65 years and older (n=54) with sensitive skin and dermatoporosis managed with twice-daily application of the cream on both forearms and 1 leg (randomly selected, with the other leg serving as control). Key assessments included transepidermal water loss (TEWL), skin thickness measurement by ultrasound, clinical scoring for dryness and roughness, a participant questionnaire, and standard safety assessments. RESULTS:Twice-daily use of the novel cream resulted in an ongoing consistent positive increase in skin thickness of 5% (P<0.05), with improvements primarily in the dermis and epidermis but also notable in the subdermal layer. Significant improvements in hydration were observed starting from Day 7 and observed through Day 84 (or end of study) (P<0.05). Changes in TEWL showed a 20% improvement in barrier function that also was apparent early (Day 7) and sustained through the study (40% improvement at day 84, P<0.05). The cream demonstrated excellent safety with no adverse reactions and no worsening in tolerability parameters. CONCLUSIONS:This cream, containing microdoses of mandelic acid and Centella asiatica, safely and effectively improved skin thickness, firmness, and resiliency, and had high acceptability with study participants. J Drugs Dermatol. 2025;24(4):352-356. doi:10.36849/JDD.8947.

BACKGROUND:Aging is associated with fat atrophy and fibrosis with loss of adipocyte differentiation from preadipocytes. New approaches to this loss involve agents that can renew the proliferative and differentiative capacities of preadipocytes with the aim of creating new healthy adipose tissue that secrete adipokines that positively impact on skin health. MATERIAL & METHODS:We investigated the effect of Magnolol (ML), a naturally derived compound, on human primary pre-adipocyte viability and proliferation as well as adipogenic gene expression and increase in lipid production. Cell proliferation was assessed using fluorescent signaling, and adipocyte differentiation was monitored by following morphological and microscopic changes. RNA purification and real-time PCR were undertaken to examine gene expression changes, and Oil red O staining was used to confirm adipose cell transformation. Adipokine expression, in particular adiponectin quantification, was also undertaken. RESULTS:Magnolol, at a relatively low concentration, demonstrated clear adipogenic activity: with a significant increase in preadipocyte proliferation after 48 h and a significant accumulation of adipocytes as demonstrated by oil red staining. Increased gene expression of PLN1 and FABP4 and a significant increase in adiponectin protein expression was demonstrated. CONCLUSION:Magnolol stimulates preadipocyte proliferation and conversion to adipokine-producing adipocytes. This has the potential for a positive skin health and volumizing effect if used in a topical formulation.

BackgroundThis study follows an initial scientific validation linking sodium ascorbate (SAC) with elastin conservation and the clinical trial histology observation that the full formulation tested there stimulated elastin development. In an effort to explain the increased elastin response, a candidate was sought that may provide synergy to SAC during elastin stimulation. Lactoferrin was the constituent chosen to explore in this realm.Materials and MethodsUsing the previously described ex vivo skin model, freshly collected discarded human skin from 2 donors was used to evaluate the effects of lactoferrin and SAC alone and together, and L-ascorbate CE Ferulic formulation (CEF) on elastogenesis. Four skin explants were topically subjected to the treatments daily for 7 days and one group was left untreated as a negative control. The tissue was fixed and embedded. Sections were evaluated by immunofluorescence using antibodies targeting Tropoelastin and CD44, with DAPI counterstaining to observe nuclei. Images were then analyzed using ImageJ.ResultsTreatment with SAC and lactoferrin demonstrated a significant synergistic effect on tropoelastin stimulation compared to the single treatments. In addition, this combination demonstrated intact and increased elastin fibers in contrast to the CEF, which portrayed fragmented elastin fibers. In addition, an additive effect of SAC also contributed to the enhanced CD44, suggesting an increased presence of hyaluronic acid, a new observation for this compound.ConclusionThis study complements a series of studies that have been undertaken to validate the efficacy of a novel antioxidant formulation. Aside from its efficacy in ROS management, the SAC constituent is unique in the different forms of Vitamin C for its ability to conserve elastin. Prior clinical studies demonstrated additive elastin stimulation on histology, not just conservation. From this current study, the combination of SAC with lactoferrin may be responsible for this additive stimulatory effect on elastin. This presents a significant advance in topical antioxidant formulations where the Vitamin C component provides antioxidant and collagen stimulation with additional elastin stimulation rather than degradation.

BACKGROUND:Dermatoporosis (DP) is a condition associated with thinning skin layers and resultant fragility. Much of the thinning is related to fibroblast dysfunction, production of destructive inflammatory cytokines, breakdown of the extracellular matrix (ECM), and weakening of the dermo-epidermal junction. A major contributor to this change in the ECM milieu, previously under-considered, is cellular senescence, particularly involving the papillary dermal fibroblasts. METHODS:A series of experiments were undertaken to explore the impact of a combination of known actives on senescent cell status. Human keratinocytes and fibroblasts were cultured, and cytotoxicity tests were performed to determine the ideal concentration to avoid cell toxicity. Microdoses of Centella asiatica (0.005%) and mandelic acid (0.05%) were found to be ideal in avoiding any cytotoxicity. However, the challenge was then to assess the efficacy of these actives in this microdosed form. After exposing the cells to the compounds, RNA was isolated and sequenced. Moreover, a well-described ex vivo model using photodamaged skin was subjected to immunofluorescence to identify senescent cells (via p16INK4a), particularly in the papillary dermis, using the microdose formulation compared to untreated skin. In addition, JAG/NOTCH expression in the epidermal basal cells was evaluated to further understand the cellular senescence signaling mechanism. RESULTS:Microdosing these two well-known agents had surprisingly significant synergistic effects in vitro, decreasing senescence-associated secretory phenotype (SASP) cytokines and the associated inflammation involved in the process. The ex vivo model revealed a significant (P<0.05) decrease in senescent cells in the papillary dermis and a significant increase (P<0.001) of JAG/NOTCH expression in the basal cells of the epidermis. CONCLUSION:Using microdoses of two known agents, a novel approach produced an unexpected effect of reversal of dermal senescent cells and promoting an anti-inflammatory milieu. A gene expression analysis of the individual and combined actives validated these observations, followed by full formulation testing in an ex vivo model. The approach of limiting cellular senescence in dermal fibroblasts for managing DP is novel and provides an exciting new direction to address dermatoporosis. Clinical studies will follow. J Drugs Dermatol. 2024;23(9):748-756. doi:10.36849/JDD.8388.