The integration of biological tissues with conducting polymers is crucial for the advancement of bioelectronics. Although the potential toxicity of some conducting-ink components is an acknowledged constraint for in vivo use, a more fundamental limitation is the lack of molecular understanding of how conducting polymers interact with biological barriers. This study addresses some of the limitations by presenting a novel method for direct polymerization of pyrrole on excised skin in vitro and investigates the evolving skin/conducting polymer interface using electrical impedance spectroscopy (EIS), X-ray diffraction, vapor sorption, and complementary analyses. Direct polymerization of pyrrole on skin is performed by applying an aqueous pyrrole solution to the dermal side and an oxidant (ferric ion solution) on the stratum corneum (SC) side of the skin membrane fixed in a Franz cell. EIS measurements show a marked reduction in skin barrier resistance after PPy formation, whereas control experiments produced the opposite trend, confirming that the resistance drop arises specifically from polymerization. Our complementary analyses indicate that polymerization is primarily localized at the solution-SC interface but also support the formation of an electrically coupled pathway across the barrier. These results provide molecular-level insight into polymer-SC interactions, imply the formation of a coherent conductive junction that extends through the SC layers, and inform the design of future skin-integrated bioelectronic materials.

Niacinamide (NIA) is a widely used skincare ingredient with established benefits for skin barrier support, inflammation reduction, and dermal health. However, the mechanisms governing its transdermal delivery remain insufficiently understood, particularly regarding how formulation pH influences its permeation through the stratum corneum (SC). This study investigates how donor phase pH (5.0 vs. 7.4) modulates NIA skin permeation and how these effects relate to pH induced changes in SC electrical properties. Franz cell diffusion experiments were combined with electrical impedance spectroscopy (EIS) using full‑thickness human skin and 3D reconstructed epidermal tissue models. Permeation was quantified over 24 h and in pH switch experiments, while EIS characterized pH dependent changes in membrane resistance (Rmem) and effective capacitance (Ceff). Additional analyses assessed microbial conversion of NIA to nicotinic acid during prolonged exposure. Neutral donor pH (7.4) increased NIA permeation by roughly twofold compared with acidic pH (5.0) in both membrane types. Correspondingly, pH 7.4 decreased Rmem and increased Ceff, indicating pH driven changes in SC lipid organization and dielectric behavior. These effects were reversible and likely stem from alterations in SC lipid domains, including pH dependent partial deprotonation of free fatty acids that modifies the continuous lipid regions and introduce localized structural microdefects. Such changes enhance NIA and ion permeability and increase SC dielectric properties at neutral pH. Although microbial conversion of NIA to nicotinic acid was negligible within the first 24 h, it became clearly detectable upon prolonged experiments. In conclusion, donor phase pH is a critical determinant of NIA skin permeation, primarily through reversible modulation of SC lipid structure and transport pathways. These findings highlight the importance of pH control in topical formulations and underscore the need to consider microbiota‑mediated transformations when evaluating the efficacy and safety of skin care products containing NIA.

Aim: Understanding the interactions between extracellular matrix (ECM) proteins and proteases is essential for elucidating the mechanisms of ECM remodeling in both health and disease. The integration of real-time, label-free, and surface-sensitive techniques based on distinct physical principles enables detailed characterization of protease activity at the ECM substrate-liquid interface. Based on these kinds of techniques, this study focuses on investigating the dynamic interactions between protein adlayers and proteases, offering new insights into complex ECM remodeling processes. Experiments: The adsorption behavior and resulting adlayer properties of collagen and elastin, used as ECM model substrates, and the proteolytic activity of collagenase and elastase, were studied using synchronized quartz crystal microbalance with dissipation monitoring (QCM-D) and localized surface plasmon resonance (LSPR). Changes in adsorbed mass, viscoelastic properties, and near-surface dielectric environment were monitored via shifts in frequency (Δf), energy dissipation (ΔD), and plasmon resonance peak (∆λ), respectively. Atomic force microscopy (AFM) was employed to validate film morphology and mechanical alterations before and after proteolytic digestion. Findings: While the QCM-D/LSPR signals both detect mass uptake during protein adsorption and mass loss during proteolysis, synchronized measurements, complemented with AFM imaging, reveal more complex responses arising from the differing surface sensitivities of the techniques. Our integrated analysis show substantial differences in adlayer morphology and proteolytic degradation. Collagen forms a vertically heterogeneous adlayer with a dense near-surface layer and a highly viscoelastic outer layer of protruding fibrils (Δf ≈ −100 to −240 Hz, ΔD ≈ 40–70 ppm, and ∆λ ≈ 0.7 nm), whereas elastin adsorbs as a thinner, more rigid film (Δf ≈ −36 to −40 Hz, ΔD ≈ 2–3 ppm, and ∆λ ≈ 0.4 nm). Real-time monitoring reveals that collagenase primarily degrades the protruding collagen fibrils, significantly affecting all QCM-D and LSPR signals—particularly showing a clear overtone dependence in ΔD and Δf shifts—while elastase digestion of elastin occurs without overtone dependence and results in more pronounced changes in Δf and ∆λ, with comparatively low effect on ΔD. Cross-reactivity experiments confirm substrate specificity; however, both proteases show non-specific activity. Inhibition studies demonstrate that QCM-D can detect both true enzymatic inactivity and substrate-inhibitor interactions that mimic inhibition in conventional assays, for example by physically adsorbing to the substrate and thereby shielding it from proteolysis.

Skin cancer is one of the most common types of cancer worldwide, with exposure to UVB radiation being a significant risk factor for its development. To prevent skin cancer, continuous research efforts have focused on finding suitable photoprotective ingredients from natural sources that are also environmentally friendly. This study aimed to develop oil-in-water photoprotective nanoemulsions containing marine macroalgae extract. A Box-Behnken experimental design was used to identify the most promising formulation composition, resulting in optimal physical properties. These properties, including droplet size, polydispersity index (PDI), and zeta potential, were evaluated using dynamic light scattering (DLS). To assess the photoprotection capacity of the formulations, electrical impedance spectroscopy (EIS) was employed to evaluate alterations in the electrical characteristics of excised pig skin membranes placed in Franz cells equipped with a 4-electrode set-up. The final composition of the nanoemulsion was caprylic/capric triglycerides 4%, Macrogolglycerol ricinoleate 30%, and algae extract 1%. The nanoemulsions had an average droplet size of 128.5 +/- 8.6 nm, a PDI of 0.25 +/- 0.06, and a zeta potential of 45.14 +/- 0.02 mV. Compared to the control group, the photoprotective capacity of the oil-in-water nanoemulsions was statistically significant. Specifically, only a 15% reduction in the skin membrane electrical resistance following UVB exposure was observed when the formulation containing algae extract was used, whereas a 50% reduction was observed for the vehicle. In conclusion, this work demonstrates that the developed nanoemulsions based on natural ingredients show promising protective capacity against UVB exposure of the skin.

Niacinamide (NIA) is widely used in skincare for its favorable safety profile, anti-aging effects, and proven clinical efficacy in treating various skin conditions. However, its direct impact on the hydration and molecular organization of the stratum corneum (SC), the primary skin barrier, remains unclear. This study examines how NIA influences the SC's lipid matrix organization, soft keratin structure, and water sorption behavior across varying relative humidity (RH) levels. Using small- and wide-angle X-ray diffraction and dynamic vapor sorption measurements, we compared NIA-treated SC samples to untreated controls under different RHs. The main findings show that while NIA is non-hygroscopic, it enhances water uptake of the SC at high humidity (95% RH). At low humidity (60% RH), NIA swells the keratin monomer spacing, although the SC water content remains low, suggesting a plasticizing effect that could increase SC flexibility in dry conditions. NIA also modifies the diffraction intensities from the lipid matrix differently at 60% and 95% RH, implying that it interacts with the SC lipid matrix and influences the water distribution within the SC lipid and protein domains. These effects appear independent of the investigated dose regime, indicating a specific concentration threshold. Overall, NIA shows distinct interaction with keratin, swelling the spacing between keratin monomers in dry conditions, without acting as a traditional keratolytic agent.

Purpose: To evade immunosurveillance many cancers convert tryptophan (Trp) into kynurenine (Kyn), which induces immunotolerance and suppresses immune responses. Elevated Kyn amounts have been found in blood from patients with cutaneous melanoma. This study aimed to investigate whether higher Kyn abundance and lower Trp abundance can be detected on the surface of cutaneous melanoma lesions compared with adjacent non-lesional skin.

Methods: Sixteen patients with suspected melanomas were enrolled in this study. All lesions were excised and histopathologically diagnosed: 7 lesions were diagnosed as invasive malignant melanomas (MM), 6 as melanomas in situ (MIS), and 3 as benign lesions (BL). Non-invasive metabolite sampling was performed by tape stripping of suspected skin lesions and adjacent healthy non-lesional (NL) skin. Trp, Kyn, tyrosine (Tyr), and phenylalanine (Phe) were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Electrical impedance spectroscopy (EIS) measurements were conducted to assess skin barrier integrity.

Results: Levels of all metabolites, Tyr (x6), Phe (x6), Trp (x5), and Kyn (x3), were significantly higher in MM lesions compared with adjacent NL skin, resulting in an elevated Trp/Kyn ratio. Trp levels increased less than Phe and Tyr levels, suggesting a potential increase in Trp depletion. Skin resistance in MM lesions was half that of NL skin. No differences were observed between MIS or BL and NL skin.

Conclusions: Non-invasive skin sampling revealed elevated Tyr, Phe, Trp and Kyn levels in MM skin, which is likely the result of compromised skin barrier at this stage of cutaneous melanoma.

Early detection of cancer via biomarkers is vital for improving patient survival rates. In the case of skin cancers, low-molecular-weight biomarkers can penetrate the skin barrier, enabling non-invasive sampling at an early stage. This study focuses on detecting tryptophan (Trp) and kynurenine (Kyn) on the surface of reconstructed 3D melanoma and melanocyte models. This is examined in connection with IDO-1 and IL-6 expression in response to IFN-γ or UVB stimulation, both crucial factors of the melanoma tumor microenvironment (TME). Using a polystyrene scaffold, full-thickness human skin equivalents containing fibroblasts, keratinocytes, and melanocytes or melanoma cells were developed. The samples were stimulated with IFN-γ or UVB, and Trp and Kyn secretion was measured using HPLC-PDA and HPLC-MS. The expression of IDO-1 and IL-6 was measured using RT-qPCR. Increased Trp catabolism to Kyn was observed in IFN-γ-stimulated melanoma and melanocyte models, along with higher IDO-1 expression. UVB exposure led to significant changes in Kyn levels but only in the melanoma model. This study demonstrates the potential of skin surface Trp and Kyn monitoring to capture TME metabolic changes. It also lays the groundwork for future in vivo studies, aiding in understanding and monitoring skin cancer progression.

Capacitive humidity sensors typically consist of interdigitated electrodes coated with a dielectric layer sensitive to varying relative humidity levels. Previous studies have investigated different polymeric materials that exhibit changes in conductivity in response to water vapor to design capacitive humidity sensors. However, lipid films like monoolein have not yet been integrated with humidity sensors, nor has the potential use of capacitive sensors for skin hydration measurements been fully explored. This study explores the application of monoolein-coated wireless capacitive sensors for assessing relative humidity and skin hydration, utilizing the sensitive dielectric properties of the monoolein-water system. This sensitivity hinges on the water absorption and release from the surrounding environment. Tested across various humidity levels and temperatures, these novel double functional sensors feature interdigitated electrodes covered with monoolein and show promising potential for wireless detection of skin hydration. The water uptake and rheological behavior of monoolein in response to humidity were evaluated using a quartz crystal microbalance with dissipation monitoring. The findings from these experiments suggest that the capacitance of the system is primarily influenced by the amount of water in the monoolein system, with the lyotropic or physical state of monoolein playing a secondary role. A proof-of-principle demonstration compared the sensor's performance under varying conditions to that of other commercially available skin hydration meters, affirming its effectiveness, reliability, and commercial viability.

Lipid membranes play a crucial role in regulating the body's water balance by adjusting their properties in response to hydration. The intercellular lipid matrix of the stratum corneum (SC), the outermost skin layer, serves as the body's primary defense against environmental factors. Osmolytes, including urocanic acid (UCA) and glycerol, are key components of the natural moisturizing factor that help the SC resist osmotic stress from dry environments. This study examines the effects of UCA and glycerol (each at 5 mol%) on isolated human SC lipids. For this, different techniques were employed, offering complementary information of the system's multiscale characteristics, including humidity-scanning quartz crystal microbalance with dissipation monitoring, infrared spectroscopy, X-ray diffraction, electrical impedance spectroscopy, and studies of water loss and permeability. Our results show that UCA increases water sorption and makes lipid films more liquid-like at high relative humidity, without significantly altering the lipid lamellar structure, chain order, or orthorhombic chain packing. Lipid films containing UCA exhibited higher water loss, significantly higher model drug permeability, and kinetically faster changes in electrical properties upon contact with aqueous solution compared to control lipids. These observations suggest that UCA reduces lipid cohesion in regions other than the acyl chain-rich leaflets, which may impact SC desquamation. In contrast, glycerol did not influence the hydration or permeability of the SC lipid matrix. However, it increased the proportion of orthorhombic domains at high humidities and slowed the kinetics of the hydration process, as evidenced by slower changes in the dielectric properties of the lipid film. These findings suggest that glycerol enhances lipid cohesion rather than increasing water uptake, which is typically the expected function of humectants. Consequently, UCA and glycerol appear to have distinct roles in maintaining epidermal homeostasis.

Introduction: To minimize the risk of developing foot-ulcers, persons with diabetes are given the advice to daily inspect their feet and to apply skincare formulations. However, commercially available skincare products have rarely been developed and evaluated for diabetes foot care specifically. The primary aim of this randomized controlled trial (RCT) is to evaluate the effects in reducing foot xerosis in persons with diabetes without footulcers using two skincare creams containing different humectants (interventions) against a cream base nonhumectant (comparator). Secondary outcomes are to evaluate differences on skin barrier integrity, lowmolecular weight biomarkers and skin microbiota, microcirculation including transcutaneous oxygen pressure, degree of neuropathy, and HbA1c between intervention-comparator creams. Methods: Two-armed double-blind RCT, registered in ClinicalTrials.gov Identifier: NCT06427889. With 80 % power, two-tailed significance of 2.5 % in each arm, 39 study persons is needed in each arm, total 78 persons, 98 including dropouts, to be able to prove a reduction of at least one category in the Xerosis Severity Scale with the intervention creams compared to the comparator. In one arm, each participant will treat one foot with one of the intervention creams (Oviderm (R) or Canoderm (R)), while the opposite foot will be treated with the comparator cream (Decubal (R) lipid cream), twice a day. If needed, participants are enrolled after a wash-out period of two weeks. The participants will undergo examinations at baseline, day 14 and day 28. Discussion: This RCT evaluate the potential effects of humectants in skin creams against foot xerosis in persons with diabetes.