Search Results (171)

Light-based therapies are becoming increasingly = more mainstream, not only within the medical science space, but also within the fields of cosmetic dermatology and personal grooming. Intense Pulsed Light (IPL) harnesses the ability of the natural chromophore–melanin to absorb light energy, which is translated into heat energy and consequently results in targeted thermolysis of cells rich in melanin. This mechanistic pathway lends itself to a wide range of applications, including long-term hair removal, skin rejuvenation, the treatment of unwanted pigmentation, and the treatment of ophthalmic conditions. The development of home use devices (HUDs) for the delivery of IPL-mediated hair removal has facilitated the self-administration of photothermal treatments and reduced reliance on clinical settings. In this study, we demonstrate a pioneering approach to model aspects of IPL-induced thermal induction and selective thermolysis in a complex human skin tissue equivalent. Our approach utilised a deactivated HUD with disabled safety features that allowed for the exposure of tissue constructs to high-fluence IPL. We demonstrate an increase in biomarkers consistent with increased cellular temperature, induction of apoptosis, and increased pro-inflammatory cytokine release following extreme treatment regimens, all of which correlate with an increased fluence and/or increased number of IPL pulses delivered. This method allowed for the identification of cellular events evoked by increasing fluence and extreme-exposure regimes. Full article

Severe skin injury in humans typically heals through fibrotic remodelling rather than true regeneration, resulting in permanent loss of appendages, sensory function, and tissue architecture. Over the past decades, advances in bulk, single-cell, and spatial transcriptomic profiling have revealed that cutaneous wound repair is governed by dynamic, context-dependent gene-regulatory programmes across epidermal, dermal, vascular, and immune compartments. These studies highlight substantial heterogeneity in keratinocyte, fibroblast, and immune cell states, and identify RNA-mediated regulatory networks that bias healing toward either regenerative or fibrotic outcomes. In parallel, stem cell-derived skin organoids and advanced engineered skin equivalents have emerged as experimental platforms capable of reproducing key aspects of human skin organisation, offering new opportunities to move beyond purely reparative grafting strategies. This review integrates evidence from human or murine skin and wound transcriptomics, RNA-based regulatory mechanisms, and organoid-based skin engineering relevant to trauma and burn reconstruction. We summarise how protein-coding and non-coding RNAs (including miRNAs and lncRNAs) coordinate epithelial migration, inflammation resolution, angiogenesis, and ECM remodelling, and how the dysregulation of these networks contributes to pathological scarring. This article synthesises transcriptomic, RNA regulatory, and skin organoid research to propose a conceptual, hypothesis-generating framework for regenerative skin repair, without claiming clinical readiness or validated therapeutic translation. Full article

Lysine carboxymethyl cysteinate (LCC) has been identified as a glutathione (GSH) precursor for the use of cosmetic products, providing a defense against oxidative stress by elevating GSH levels, and mitigating UVB-induced pigmentation and barrier disruption. In this study, the protective efficacy of LCC on epidermal barrier integrity under UVB irradiation was systematically evaluated and its underlying mechanisms were investigated. Results from the UVB-exposed 3D living skin equivalent model (LSE) indicated that LCC effectively restored UVB-induced reductions in epidermal living cell thickness by 9.67%. In addition, LCC markedly increased the expression of key biomarkers related to cornified envelope (CE) formation and skin hydration, including transglutaminase 1, involucrin, loricrin and aquaporin 3 by 104.80%, 121.67%, 218.63% and 388.39%, respectively, compared with the UVB group. Transcriptomics analysis in human primary keratinocytes further revealed that LCC regulated multiple biological functions, including glutathione synthesis pathway, oxidation response, inflammatory process, and notably autophagy. After confirming LCC’s potential in boosting autophagy-associated gene expression (p-value < 0.05) and autophagy activity (p-value < 0.01) in keratinocytes, functional validation in the same model confirmed that LCC counteracted UVB-induced suppression of genes involved in barrier formation, particularly those associated with CE development and autophagy, while these protective effects were abolished by chloroquine, an autophagy inhibitor. Findings from the UVB-exposed LSE model further substantiated this mechanism. Collectively, these results demonstrate that LCC safeguards the epidermis from UVB-induced cornification abnormalities through the activation of autophagy. Full article

Gesture recognition with electrical impedance tomography (EIT) is an enormous potential tool for human–machine interaction because of its low cost, low complexity and high temporal resolution. Although high-precision EIT-based gesture recognition has been achieved in ideal scenarios, ensuring its consistent performance under interference remains challenging. This article presents a novel method to alleviate the effect of confounding factors on EIT gesture recognition. An EIT armband was designed to mitigate the effect of contact impedance variation based on equivalent circuit analysis, and a spatial–temporal fusion network, named the Fold Atrous Spatial Pyramid Pooling-Gated Recurrent Unit (FASPP-GRU), was developed for robust gesture classification. The results showed that the proposed two-layer electrode maintained a stable contact impedance when its contact force with the skin was changed. Although confounding factors caused significant changes in baseline forearm impedance, FASPP-GRU achieved 80% accuracy under the effect of limb position changes and dynamic changes in muscle state over time, which outperforms conventional classifiers. With an 87 μs inference time, the proposed system shows enormous potential in real-time applications. Full article

Advances in regenerative medicine increasingly rely on human-relevant in vitro systems to model the multistage process of wound healing. However, the translation of research into effective therapies remains limited by the inability of traditional 2D cultures and animal models to faithfully replicate the structural and biochemical complexity of human skin. While existing reviews often focus on the structural composition of static skin equivalents, this review addresses a critical knowledge gap: the need for dynamic, time-dependent methodologies that can capture the spatiotemporal evolution of healing, from inflammation to remodeling, in both physiological and pathological conditions. To this end, we critically evaluate next-generation platforms, including 3D bioprinting, organ-on-chip systems, organoids, and iPSC-based models, highlighting their comparative advantages and technical hurdles like vascularization and scalability. The unique contribution of this work lies in providing a forward-looking framework that advocates for the convergence of bioengineering and computational modeling to move beyond “steady-state” snapshots toward predictive, high-resolution dynamic models. We conclude that the future of wound healing research depends on integrating vascular and immune components within these platforms to achieve truly human-relevant, personalized diagnostic and therapeutic tools. Full article

The brewing process generates substantial by-products rich in potentially bioactive compounds (e.g., polyphenols and fermentation metabolites), providing a sustainable and appealing source of cosmetic ingredients. Oil-in-water (O/W) emulsions containing 20% (w/w) aqueous extracts from Bionda Triplo Malto beer, wort, and key brewing by-products (hops, yeast, and spent grain) were developed and evaluated using a combined in vitro–in vivo approach. Aqueous extracts were first screened on human immortalized dermal fibroblasts (BJ-5ta) at 0.25–1 mg/mL for cytocompatibility and antioxidant activity. Within this concentration range, no significant changes in cell viability or intracellular antioxidant capacity under UV stress were detected, suggesting cytocompatibility but limited inherent activity. When incorporated into O/W emulsions and tested at an active-equivalent concentration of 10 mg/mL, the formulations increased fibroblast metabolic activity and antioxidant response. In contrast, free extracts at 10 mg/mL showed concentration-dependent cytotoxicity for some matrices, with beer- and yeast-based emulsions demonstrating the strongest effects. The emulsions exhibited good physicochemical stability (pH ~5.7–6.2; viscosity 4750–5150 mPa·s), passed the ISO 11930:2012 challenge test, and were well tolerated in patch testing. In a double-blind, randomized split-forearm study on 50 healthy volunteers over 30 days, beer, yeast, and spent grain-based formulations improved skin parameters versus baseline. TEWL decreased (e.g., beer: 16.22 ± 5.12 to 10.77 ± 2.22 mg·m⁻²·h⁻¹; yeast: 16.29 ± 5.66 to 10.18 ± 1.08; spent grain: 14.45 ± 4.34 to 11.66 ± 2.28), hydration increased (beer: 35.15 ± 5.93 to 42.26 ± 3.78; yeast: 33.27 ± 4.87 to 42.92 ± 2.48; spent grain: 34.22 ± 5.19 to 41.16 ± 3.17, and elasticity improved for beer and yeast formulations (62.33 ± 3.27 to 70.24 ± 2.12 N/m) and yeast (61.21 ± 4.72 to 72.13 ± 5.55 N/m). Based on these findings, brewing-derived ingredients demonstrate potential as cosmetic actives, with formulation critically determining their clinical efficacy. Full article

The field of experimental radiooncology and the quality assessment (QA) aimed at patient safety both profit from the utilisation of biomimetic principles. The work with phantoms based on biological structures of animals or humans, utilising the principles of anatomic mimicry, has a long tradition in radiotherapy research. When phantoms are produced from tissue-equivalent materials, they mimic the radiological properties of tissues and organs, allowing researchers and clinicians to study dose distribution and optimise treatment plans without exposing real patients to radiation. Biomechanical mimicry would take this a step further by creating phantoms that replicate the movement and deformation of organs during physiological movement, such as heartbeat or breathing, enabling a more accurate simulation of dynamic treatment scenarios. Bioinspired sensor technologies, such as artificial skin or integrated detectors, can be used to monitor radiation exposure, organ motion or temperature changes during therapy with high precision. The utility of such a phantom could be further enhanced by creating a realistic tumour microenvironment as an irradiation target, following the principles of microenvironmental biomimicry. Thus, biomimetic strategies can be exploited in the validation of radiotherapy technologies and open new perspectives for adaptive radiotherapy and real-time monitoring. Full article

Background: Centaurium erythraea Rafn. (C. erythraea) is a medicinal plant traditionally used in European folk medicine for the treatment of wounds, skin inflammations, and other dermatological conditions, in addition to its well-documented systemic antioxidant and anti-inflammatory effects. However, its topical applications remain insufficiently investigated, particularly using plant material collected from Romania. The purpose of this study was to prepare different ointment formulations containing C. erythraea Rafn. extract obtained from the aerial parts of the plant, using various excipients, and to evaluate their in vitro and in vivo efficacy. Methods: The phytochemical profile of C. erythraea extract was characterized using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The lyophilized extract was pre-dissolved in different solubilizing agents—Transcutol^® P (diethylene glycol monoethyl ether), Capryol^® 90 (propylene glycol monocaprylate), or a combination of both—and then incorporated into five ointment formulations. Texture analysis and an in vitro membrane diffusion study were performed. The antioxidant capacity of the formulations was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and total phenolic content (TPC) assays. Anti-inflammatory activity was evaluated in vitro using tumor necrosis factor-alpha (TNF-α)-induced interleukin-1 beta (IL-1β) production in human keratinocyte (HaCaT) cells, and in vivo using a carrageenan-induced rat paw edema model. Results: LC–MS/MS identified 18 polyphenolic compounds, with hyperoside (3.78 ± 0.05 µg/mL), protocatechuic acid (1.13 ± 0.06 µg/mL), chlorogenic acid (1.07 ± 0.06 µg/mL), and quercetin (0.53 ± 0.03 µg/mL) as the principal constituents. The formulation containing both Transcutol^® P and Capryol^® 90 exhibited the most pronounced antioxidant activity (65% DPPH inhibition; 69.71 ± 0.83 mg gallic acid equivalent/mL) and significantly reduced IL-1β levels by 45.7% compared to the inflamed control. In vivo, this formulation showed comparable anti-edematous effects to a methylprednisolone ointment. Furthermore, it demonstrated the highest skin permeation efficiency, with a quercetin diffusion coefficient of 35.12 × 10⁻⁵ cm²/min. Conclusions: These findings highlight the therapeutic potential of C. erythraea extract from aerial parts in topical formulations and underscore the enhancing role of Transcutol^® P and Capryol^® 90 in improving both the pharmacodynamic and pharmacokinetic properties of bioactive compounds. Full article

This study examines the biocompatibility of 11 modern wound dressings (WDs)―Syspur-derm^®, Parapran^®, Lomatuell^®H, Voskopran^®, Metalline^®, Granuflex^®, Chitopran^®, HydroTac^®transparent, Branolind^®N, Aquacel^TM adhesive foam, Aquacel^TMAg⁺―developed for the treatment of acute and chronic wounds, and their potential use as secondary WD for the hydrogel-based bioengineered skin equivalent (BSE) “Equivalent Dermal, ED”. The study was conducted to better understand the properties of these WDs that influence the healing process. The biocompatibility of WDs was evaluated in vitro based on their effects on the viability of human dermal fibroblasts (DFs). The MTT assay, lifetime analysis of DFs’ morphological state, and analysis of their actin cytoskeletal organization using a WDs’ extracts showed that effects of WD on DFs varied among WDs. It has been revealed that WDs Parapran^®, Lomatuell^®H, Voskopran^®, Metalline^® and Chitopran^® have high biocompatibility and can be effectively used for wound treatment, whereas Granuflex^®, Syspyr-derm^®, HydroTac^® transparent, Branolind^®N, Aquacel^TM adhesive foam and Aquacel^TMAg⁺ have lower biocompatibility, so they could be used for wound therapy with caution. Only Parapran^® with chlorhexidine showed high biocompatibility with the BSE “The Dermal Equivalent, ED” and can be safely used in combination with it as a secondary WD. Full article

Despite advancement in skin engineering, native skin grafting remains the gold standard in clinical settings. We have previously demonstrated that a platelet-derived hydrogel (PG) can act as a scaffold to engineer a semi-mature bilaminar human skin equivalent (PG-HSE). In this study, PG-HSE was grafted on full thickness wounds in athymic mice. PG-HSE was compared with native skin autografts and a clinically proven bilaminar skin graft that utilises a single layer NovoSorb^® polyurethane biodegradable temporising matrix (plus plasma) as the scaffold (BTM-HSE). The graft analysis revealed PG-HSE-grafted wounds were fully epidermised in two weeks and the level of inflammatory markers, CXCl1, CXCl2, IL1β, and IL-6 transcripts, in grafts were at similar levels to their levels in autografts. This coincided with higher expression of COL1A2, COL3A1, and COL5A1 transcripts in PG-HSE grafts, compared to autografts and BTM-HSE grafts. Moreover, a higher deposition of both Col I and Col III was detected in the PG-HSE graft wound bed, when compared to the BTM-HSE graft wound bed. Conversely, BTM-HSE grafts showed a higher level of integrins, ITGA2, ITGA3, ITGA5, ITGA6, ITGAV, and ITGB1, at the RNA level, suggesting a stronger cell–scaffold interaction. In summary, we have shown although both PG and single layer BTM foam (plus plasma) are effective scaffolds for skin engineering, some key aspects of wound repair, including a reduction in inflammation and an increase in collagen deposition, are achieved with the platelet-derived hydrogel. The long-term effect of these scaffolds on wound scarring remains to be investigated. Full article

The bark of Dillenia indica L. is a rich source of phenolic and triterpenoid compounds, including betulinic acid (BA), known for their antioxidant and anti-aging properties. This study investigated the antioxidant potential of a BA-enriched extract through a multidisciplinary approach combining computational, experimental, and cell-based evaluations. Molecular docking and molecular dynamics simulations revealed that BA binds stably to Kelch-like ECH-associated protein 1 (KEAP1), suggesting activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Extraction conditions were optimized using response surface methodology (RSM) and artificial neural network (ANN) modeling, yielding the maximum total phenolic content (TPC; 85.33 ± 2.26 mg gallic acid equivalents/g) and total flavonoid content (TFC; 75.60 ± 1.66 mg catechin equivalents/g), with ANN demonstrating superior predictive performance compared to RSM. Electrospray ionization tandem mass spectrometry (ESI-MS/MS) confirmed the presence of BA in the optimized extract. Simulated gastrointestinal digestion revealed reductions in TPC, TFC, and radical scavenging activity during the gastric phase. In ultraviolet B (UVB)-irradiated human keratinocyte (HaCaT) cells, the optimized extract significantly reduced intracellular reactive oxygen species (ROS) and upregulated the KEAP1-Nrf2-heme oxygenase-1 (HO-1) pathway, confirming its antioxidant mechanism. These findings highlight the extract’s stability, bioactivity, and mechanistic efficacy, supporting its application as a nutraceutical ingredient for combating oxidative stress and skin aging. Full article

Congenital ichthyoses, now grouped under the acronym EDD (Epidermal Differentiation Disorders), include nonsyndromic forms (nEDD) that may be caused by loss-of-function mutations in the CDSN gene encoding corneodesmosin (CDSN-nEDD, formerly Peeling skin syndrome type 1). It is characterized by skin peeling, inflammation, itching and food allergies, while no specific therapy is currently available. High levels of KLK5, the serine protease that initiates the desquamation cascade, are found in the epidermis of CDSN-nEDD patients. Thus, we hypothesized that KLK5 inhibition would alleviate the symptoms of CDSN-nEDD and could serve as a new pharmacological target. A human epidermal equivalent (HEE) model for CDSN-nEDD was developed using shRNA-mediated CDSN knockdown. This model was characterized and used to assess the role of KLK5 knockdown on CDSN-nEDD. Also, Klk5^−/− mice were crossed with Cdsn^epi−/− mice, the murine model of CDSN-nEDD, to examine in vivo the effect(s) of Klk5 deletion in CDSN-nEDD. Both models recapitulated the CDSN-nEDD desquamating phenotype. Elimination of KLK5 aggravated the CDSN-nEDD phenotype. Epidermal proteolysis was surprisingly elevated, while severe ultrastructural (corneo)desmosomal alterations increased epidermal barrier permeability and stratum corneum detachment was manifested. Based on these results, we concluded that targeting epidermal proteolysis with KLK5 ablation cannot compensate for the loss of corneodesmosin and rescue over-desquamation of the CDSN-nEDD. Possibly, in the absence of KLK5, other proteases take over which increases the severity of over-desquamation in CDSN-nEDD. The translational outcome is that over-desquamation may not always be rescued by eliminating epidermal proteolysis, but fine protease modulation is more likely required. Full article

This study presents a comprehensive evaluation and an equivalent circuit modeling of the skin–electrode impedance characteristics of three types of ultra-thin tattoo electrodes, all based on Parylene C nanofilms but with different active materials: Gold, Silver, and PEDOT:PSS. Their performance was compared to standard disposable Ag/AgCl electrodes. Impedance measurements were carried out on six human subjects under controlled conditions, assessing the frequency response in the range of 20 Hz to 1 kHz. For each subject, the impedance was recorded six times over one hour to investigate the stability and the temporal performance. The collected data were subsequently analyzed to model the electrical properties and interface behavior of each electrode type. The findings demonstrate that the tattoo electrodes offer impedance levels comparable to those of Ag/AgCl electrodes (in the order of tens of kΩ at 20 Hz), while providing additional benefits such as enhanced conformability, improved skin adhesion, and reduced skin irritation during use. Furthermore, the modeling of the skin–electrode interface through a more detailed equivalent circuit than the single time constant model enables a more detailed interface analysis and description, with fitting algorithm R² scores of about 0.999 and 0.979 for the impedance magnitude and impedance phase, respectively. The proposed equivalent circuit offers valuable insights for optimizing electrode design, supporting the potential of Parylene C-based tattoo electrodes as promising alternatives for next-generation wearable bioelectronic applications. Full article

Tissue engineering enables autologous reconstruction of human tissues, addressing limitations in tissue availability and immune compatibility. Several tissue engineering techniques, such as self-assembly, rely on or benefit from extracellular matrix (ECM) secretion by fibroblasts to produce biomimetic scaffolds. Models have been developed for use in humans, such as skin and corneas. Ascorbic acid (vitamin C, AA) is essential for collagen biosynthesis. However, AA is chemically unstable in culture, with a half-life of 24 h, requiring freshly prepared AA with each change of medium. This study aims to demonstrate the functional equivalence of 2-phospho-L-ascorbate (2PAA), a stable form of AA, for tissue reconstruction. Dermal, vaginal, and bladder stroma were reconstructed by self-assembly using tissue-specific protocols. The tissues were cultured in a medium supplemented with either freshly prepared or frozen AA, or with 2PAA. Biochemical analyses were performed on the tissues to evaluate cell density and tissue composition, including collagen secretion and deposition. Histology and quantitative polarized light microscopy were used to evaluate tissue architecture, and mechanical evaluation was performed both by tensiometry and atomic force microscopy (AFM) to evaluate its macroscopic and cell-scale mechanical properties. The tissues produced by the three ascorbate conditions had similar collagen deposition, architecture, and mechanical properties in each organ-specific stroma. Mechanical characterization revealed tissue-specific differences, with tensile modulus values ranging from 1–5 MPa and AFM-derived apparent stiffness in the 1–2 kPa range, reflecting the nonlinear and scale-dependent behavior of the engineered stroma. The results demonstrate the possibility of substituting AA with 2PAA for tissue engineering. This protocol could significantly reduce the costs associated with tissue production by reducing preparation time and use of materials. This is a crucial factor for any scale-up activity. Full article

Plasma-derived fibrin hydrogels are widely used in tissue engineering because of their excellent biological properties. Specifically, human plasma-derived fibrin hydrogels serve as 3D matrices for autologous skin graft production, skeletal muscle repair, and bone regeneration. Nevertheless, for advanced applications such as in vitro skin equivalents and engineered grafts, the intrinsic limitations of native fibrin hydrogels in terms of long-term mechanical stability and resistance to degradation need to be addressed to enhance the usefulness and application of these hydrogels in tissue engineering. In this study, we chemically modified plasma-derived fibrin by incorporating succinimidyl alginate (SA), a version of alginate chemically modified to introduce reactive succinimidyl groups. These NHS ester groups (N-hydroxysuccinimide esters), attached to the alginate backbone, are highly reactive toward the primary amine groups present in plasma proteins such as fibrinogen. When mixed with plasma, the NHS groups covalently bond to the amine groups in fibrin, forming stable amide linkages that reinforce the fibrin network during hydrogel formation. This chemical modification improved mechanical properties, reduces contraction, and enhanced the stability of the resulting hydrogels. Hydrogels were prepared with a final fibrinogen concentration of 1.2 mg/mL and SA concentrations of 0.5, 1, 2, and 3 mg/mL. The objective was to evaluate whether this modification could create a more stable matrix suitable for supporting skin tissue development. The mechanical and microstructure properties of these new hydrogels were evaluated, as were their biocompatibility and potential to create 3D skin models in vitro. Dermo-epidermal skin cultures with primary human fibroblast and keratinocyte cells on these matrices showed improved dermal stability and better tissue structure, particularly SA concentrations of 0.5 and 1 mg/mL, as confirmed by H&E (Hematoxylin and Eosin) staining and immunostaining assays. Overall, these results suggest that SA-functionalized fibrin hydrogels are promising candidates for creating more stable in vitro skin models and engineered skin grafts, as well as for other types of engineered tissues, potentially. Full article