Natural Human Skin Research Articles

Multimodal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine.

The field of drug development is witnessing a remarkable surge in the development of innovative strategies. There is a need to develop technological platforms capable of generating human data prior to progressing to clinical trials. Here we introduce a new flexible solution designed for the comprehensive monitoring of the natural human skin ecosystem's response to immunogenic drugs over time. Based on unique bioengineering to preserve surgical resections in a long survival state, it allows for the first time a comprehensive analysis of resident immune cells response at both organ and single-cell levels. Upon injection of the mRNA-1273 COVID-19 vaccine, we characterized precise sequential molecular events triggered upon detection of the exogenous substance. The vaccine consistently targets DC/macrophages and mast cells, regardless of the administration route, while promoting specific cell-cell communications in surrounding immune cell subsets. Given its direct translational relevance, this approach provides a multiscale vision of genuine human tissue immunity that could pave the way toward the development of new vaccination and drug development strategies.

Conductive Hyaluronic Acid/Deep Eutectic Solvent Composite Hydrogel as a Wound Dressing for Promoting Skin Burn Healing Under Electrical Stimulation.

Burns can cause severe damage to the skin due to bacterial infection and severe inflammation. Although conductive hydrogels as electroactive burn-wound dressings achieve remarkable effects on accelerating wound healing, issues such as imbalance between their high conductivity and mechanical properties, easy dehydration, and low transparency must be addressed. Herein, a double-network conductive eutectogel is fabricated by integrating polymerizable deep eutectic solvents (PDESs)including acrylamide/choline chloride/glycerol (acrylamide-polymerization crosslink) and thiolated hyaluronic acid (disulfide-bonding crosslink). The introduction of PDESs provides the eutectogel with a conductivity (up to 0.25 S·m-1) and mechanical strength (tensile strain of 59-77%) simulating those of natural human skin, as well as satisfactory tissue adhesiveness, self-healing ability, and antibacterial properties. When combined with exogenous electrical stimulation, the conductive eutectogel exhibits the ability to reduce inflammation, stimulate cell proliferation and migration, promote collagen deposition and angiogenesis, and facilitate skin tissue remodeling. This conductive eutectogel shows great potential as a dressing for healing major burn wounds.

Outstanding Synergy of Sensitivity and Linear Range Enabled by Multigradient Architectures.

Flexible pressure sensors are devices that mimic the sensory capabilities of natural human skin and enable robots to perceive external stimuli. One of the main challenges is maintaining high sensitivity over a broad linear pressure range due to poor structural compressibility. Here, we report a flexible pressure sensor with an ultrahigh sensitivity of 153.3 kPa-1 and linear response over an unprecedentedly broad pressure range from 0.0005 to 1300 kPa based on interdigital-shaped, multigradient architectures, featuring modulus, conductivity, and microstructure gradients. Such multigradient architectures and interdigital-shaped configurations enable effective stress transfer and conductivity regulation, evading the pressure sensitivity-linear range trade-off dilemma. Together with high pressure resolution, high frequency response, and good reproducibility over the ultrabroad linear range, proof-of-concept applications such as acoustic wave detection, high-resolution pressure measurement, and healthcare monitoring in diverse scenarios are demonstrated.

Constructing epidermal rete ridges using a composite hydrogel to enhance multiple signaling pathways for the maintenance of epidermal stem cell niche.

The undulating microstructure rete ridge (RR) located at the junction between the dermis and epidermis plays a crucial role in improving skin mechanical properties and maintaining skin homeostasis. However, the investigation of RR microstructures is usually neglected in current tissue engineering for skin regeneration. Here, to create an epidermal model with RR microstructures, keratinocytes were cultured on a patterned GelMA-PEGDA hydrogel constructed using molding technology. Furthermore, grafting acryloylated Arg-Gly-Asp (RGD) peptides on the hydrogel surface significantly improved cell adhesion, fusion, and development. RT-PCR, Western blot, and immunofluorescence staining confirmed that cells on RR microstructures exhibited higher gene and protein expression associated with epidermal stem cells. RNA sequencing analysis of cells on RR microstructure showed higher gene expression profiles related to stem cell maintenance, basement membrane formation, and epidermal development. Furthermore, RT-PCR analysis of epidermal models of various dimensions demonstrated that smaller microstructures were more conducive to epidermal stem cell marker gene expression, which is analogous to human skin. Overall, we have successfully developed a method for integrating RR microstructures into an epidermal model that mimics natural skin to maintain epidermal stem cell niche, providing a valuable reference for researching skin regeneration within the fields of tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE: This study presents a method for precisely fabricating microstructures of skin rete ridges using composite hydrogels, thereby creating a skin model that mimics natural human skin. The findings reveal that this microstructure provides a stem cell niche that regulates the pathways and promotes the expression of proteins related to epidermal stem cells. This work advances the functional properties of tissue engineered skin and holds promise for improving the therapeutic efficacy of artificial skin grafts for the skin wounds.

P13-07: High-dimensional profiling of immune response to vaccines using bio-stabilized and injectable natural human skin

P13-07: High-dimensional profiling of immune response to vaccines using bio-stabilized and injectable natural human skin

P13-05: Automated prediction of drug reactogenicity at the site of injection, by combining natural human skin and computational inference of biological pathways

P13-05: Automated prediction of drug reactogenicity at the site of injection, by combining natural human skin and computational inference of biological pathways

The assessment of natural human skin tension orientation and its variation according to age for two body areas: Forearm and thigh

Human skin has a complex multilayer structure consisting of non-homogeneous, non-linear, viscoelastic and anisotropic materials subjected to in vivo natural pre-tension. This natural tension stems from networks of collagen and elastin fibers. The 3D organization of the collagen and elastin fibers underpins the multidirectional natural tensions in the skin volume while the state of the networks formed influences the surface topography of the skin. This topography depends on the area of the body and on the age of the person. Experiments reported in the literature have been performed ex vivo or on cadavers. By contrast, this work proposes the characterization of the anisotropic natural tension of the human skin in vivo.Experimental tests were performed on the forearms and thighs of 42 female volunteers representing two age groups [20 - 30] and [45–55] years old. Non-contact impact tests and skin-folding tests were conducted using devices developed at the LTDS (Lyon, France). The impact test generated a Rayleigh wave that spread in the skin. The speed of this wave was measured in 7 directions to study the anisotropy of the skin tension. The image of the skin relief at rest and during the skin folding test was reconstructed by optical confocal microscopy and provided the density of the skin lines printed on the outer surface of the skin. Skin folding test enables the clinician's manual procedure to be instrumented to identify tension lines i.e., Langer lines, for better healing during a surgical procedure.The main directions of natural skin tension deduced from the measured wave speed and the densities of skin lines were [40°–60°] for the forearm and [0°–20°] for the thigh, considering that the longitudinal axis of the body is situated at 90° and the transversal axis at 0°.This method shows the remarkable effect of age and body area on the mechanical behavior of human skin in vivo. The elastic properties and natural tension of the skin decrease with age. This decrease is greater in the directions orthogonal to the skin’s tension lines, leading to the accentuation of the anisotropic behavior of the cutaneous tissue. The main direction of skin tension is highly dependent on the area of the body and is directed towards a preferred direction which corresponds to the main direction of skin tension.

Inactivation of the Response Regulator AgrA Has a Pleiotropic Effect on Biofilm Formation, Pathogenesis and Stress Response in Staphylococcus lugdunensis.

ABSTRACTStaphylococcus lugdunensis is a coagulase-negative Staphylococcus that emerges as an important opportunistic pathogen. However, little is known about the regulation underlying the transition from commensal to virulent state. Based on knowledge of S. aureus virulence, we suspected that the agr quorum sensing system may be an important determinant for the pathogenicity of S. lugdunensis. We investigated the functions of the transcriptional regulator AgrA using the agrA deletion mutant. AgrA played a role in cell pigmentation: ΔargA mutant colonies were white while the parental strains were slightly yellow. Compared with the wild-type strain, the ΔargA mutant was affected in its ability to form biofilm and was less able to survive in mice macrophages. Moreover, the growth of ΔagrA was significantly reduced by the addition of 10% NaCl or 0.4 mM H2O2 and its survival after 2 h in the presence of 1 mM H2O2 was more than 10-fold reduced. To explore the mechanisms involved beyond these phenotypes, the ΔagrA proteome and transcriptome were characterized by mass spectrometry and RNA-Seq. We found that AgrA controlled several virulence factors as well as stress-response factors, which are well correlated with the reduced resistance of the ΔagrA mutant to osmotic and oxidative stresses. These results were not the consequence of the deregulation of RNAIII of the agr system, since no phenotype or alteration of the proteomic profile has been observed for the ΔRNAIII mutant. Altogether, our results highlighted that the AgrA regulator of S. lugdunensis played a key role in its ability to become pathogenic.IMPORTANCE Although belonging to the natural human skin flora, Staphylococcus lugdunensis is recognized as a particularly aggressive and destructive pathogen. This study aimed to characterize the role of the response regulator AgrA, which is a component of the quorum-sensing agr system and known to be a major element in the regulation of pathogenicity and biofilm formation in Staphylococcus aureus. In the present study, we showed that, contrary to S. aureus, the agrA deletion mutant produced less biofilm. Inactivation of agrA conferred a white colony phenotype and impacted S. lugdunensis in its ability to survive in mice macrophages and to cope with osmotic and oxidative stresses. By global proteomic and transcriptomic approaches, we identified the AgrA regulon, bringing molecular bases underlying the observed phenotypes. Together, our data showed the importance of AgrA in the opportunistic pathogenic behavior of S. lugdunensis allowing it to be considered as an interesting therapeutic target.

Particulate matter 2.5 induced hyperpigmentation in reconstructed human epidermis model (MelaKutis®).

Particulate matter 2.5 induced hyperpigmentation in reconstructed human epidermis model (MelaKutis®).

Low-Temperature tolerance and conformal adhesion zwitterionic hydrogels as electronic skin for strain and temperature responsiveness

Flexible electronics have been extensively explored for health monitoring, artificial intelligence, and soft robotics. However, it remains challenging to simultaneously achieve temperature and strain monitoring over a wide perception range that are highly analogous to natural human skin. Herein, an intelligent thermosensation zwitterionic hydrogel with superior low-temperature tolerance and conformal adhesion was successfully prepared for strain-temperature dual-modal sensors, based on the temperature-dependent self-association interactions of sulfobetaine methacrylate (SBMA) polymer chains and the incorporation of thermosensitive TEMPO-oxidized cellulose/polyaniline nanofibers (CPA NFs) in glycerol-water binary solvent system. Significantly, the TEMPO-oxidized cellulose acting as the reinforced skeleton guided the in-situ polymerization of polyaniline, while the tunneling current activated by thermal vibration of CPA NFs and the charge transfer caused by the spatial position adjustment collectively contributed to the superimposed signal recognition ability. By leveraging the glycerol molecules to inhibit the ice crystal growth without the compromise of flexibility (1095 %), strain sensitivity (GF = 1.25), and thermal responsiveness (TCR = 2.01% °C−1), the accurate determination paradigm for dual-modal strain and temperature sensor over a wide temperature range (-40–80 °C) was subtlyachieved. Additionally, we corroborated that the conformal adhesion between zwitterionic active sites (e.g. –N+(CH3)3 or -SO3-) and dynamic interfaces was critical for minimizing interface slippage and delamination, as well as maintaining real-time electricalsignal stability. The assembled zwitterionic epidermis sensor array that conformally adhered to fingers could realize the subtle signal identification and localized temperature detection, which presented promising prospects for designing the multi-modal skin-like responsiveness electronic skins that suitable for harsh temperature conditions.

Rapid water-responsive shape memory films for smart resistive bending sensors

Development of multi-functional water-sensitive shape memory material is crucial for applications in smart textiles, artificial intelligence, and biomedical areas. However, it remains a great challenge to achieve good biocompatibility, rapid water response, and robust mechanical strength in one single material. In this respect, we report a green approach to produce a series of multi-functional water-sensitive memory films (named MCP films) from sisal cellulose microcrystals (MSF-g-COOH), peach gum polysaccharide (PGP), citric acid (CA), and graphene nanosheets (GN). After crosslinking with CA, MCP films exhibit excellent water-induced shape memory and rapid pH stimulus response. More importantly, MCP films can effectively amplify different external motion stimuli by converting them into independent electrical signals to achieve accurate and continuous perception of bending. A high-performance resistive bending sensor was further fabricated from the MCP films to mimic natural human skin. The resistive bending sensor exhibited excellent water-responsive shape memory, self-adhesion, and bending sensitivity, which can be used in electronic skin, human-machine interactions, intelligent wearable devices, personalized health monitoring and other applications. Our work successfully demonstrates the application of the water-sensitive shape memory films in electronic skin and health-monitoring components, and fills the gap between material design and high-performance devices.

A Potentiometric Electronic Skin for Thermosensation and Mechanosensation

AbstractElectronic skins (e‐skins) that mimic the thermosensation and mechanosensation functionalities of natural skin are highly desired for the emerging fields of prosthetics and robotics. Advances in the materials and architecture of e‐skins have been made; nevertheless, sensing mechanism innovations are rarely explored. Here, inspired by the skin sensory behaviors, a single potentiometric sensing scheme for both thermosensation and mechanosensation functionalities are presented. Through careful materials selection, component optimization, and structure configuration, the coupling effect between thermosensation and mechanosensation can be significantly minimized. Such a potentiometric sensing scheme enables one to create a new class of energy‐efficient e‐skin with distinctive characteristics that are highly analogous to those of natural human skin. The e‐skin reported here features ultralow power consumption (at nanowatt level), greatly simplified operation (only voltage output), ultrahigh sensitivity (non‐contact sensing capability), all‐solution‐processing fabrication, and, more importantly, good capability for simultaneous monitoring/mapping of both thermal and mechanical stimulations. In addition to proposing a new sensory mechanism, integration of the dual‐functional e‐skin with a soft robotic gripper for object manipulation is demonstrated. The presented concise yet efficient sensing scheme for both thermosensation and mechanosensation opens up previously unexplored avenues for the future design of skin prosthetics, humanoid robotics, and wearable electronics.

Modified natural rubber glove with spent coffee grounds for prothesis arm cover

In this research, we developed modified rubber gloves that could cover prosthetic arms manufactured from Fused Deposition Modeling (FDM) 3D printing. FDM can produce customized prosthetic arms that are lightweight and fit the individual needs of patients. Currently, the gloves used to cover prosthetic arms are made from flexible and soft material such as silicone or polyurethane. In these studies, were use natural rubber latex (NR) to produce rubber gloves, that enhance the physical appearance of the prosthetic arm, producing a similar color and detail to the patients arm. The glove color was improved by mixing with spent coffee grounds (SCG) to produce a similar color to that of natural human skin. Moreover, SCG was not only used as a color pigment, it also contains coffee oil that creates a glossy textured on the surface similar to silicone oil. The modification process of NR used a SCG dispersion solution mixed with NR. Rubber gloves were prepared by a dipping process and use sulfur vulcanization at 75 °C, for 2 h in a hot air oven. The specimens were characterization by physical (morphology, color parameter, and %swelling), mechanical (tensile test) and thermal properties. Furthermore, the SCG can be used as a filler in natural rubber due to rubber-filler interactions that improve the tensile strength of the rubber glove with the SCG particles having a good distribution in the rubber phase. The SCG can improve the ageing stability (under 70 °C and Fluorescent light) of the rubber gloves as represented by the color parameter and tensile properties. After ageing showed a small difference in color parameter and a slight decrease in the tensile properties when greater amounts of SCG was presented in the rubber phase. Moreover, this can increase the economic value of natural rubber and spent coffee grounds in Thailand.

Fabrication of Second Skin from Keratin and Melanin.

Second skin is a topically applied, skin-conforming material that mimics human skin properties and bears potential cosmetic and e-skin applications. To successfully integrate with natural skin, characteristics such as color and skin features must be matched. In this work, we prepared bio-based skin-like films from cross-linked keratin/melanin films (KMFs), using a simple fabrication method and non-toxic materials. The films retained their stability in aqueous solutions, showed skin-like mechanical properties, and were homogenous and handleable, with non-granular surfaces and a notable cross-linked structure as determined by attenuated total reflection (ATR). In addition, the combination of keratin and melanin allowed for adjustable tones similar to those of natural human skin. Furthermore, KMFs showed light transmittance and UV-blocking (up to 99%) as a function of melanin content. Finally, keratin/melanin ink (KMI) was used to inkjet-print high-resolution images with natural skin pigmented features. The KMFs and KMI may offer advanced solutions as e-skin or cosmetics platforms.

Artificial skin through super-sensing method and electrical impedance data from conductive fabric with aid of deep learning

Sense of touch is a major part of man’s communication with their environment. Artificial skins can help robots to have the same sense of touch, especially for their social interactions. This paper presents a pressure mapping sensing using piezo-resistive fabric to represent aspects of the sense of touch. In past few years’ electrical impedance tomography (EIT) is considered to be able offer a good alternative for artificial skin in particular for its ease of adaptation for large area skin compared to individual matrix based sensors. The EIT has also very good temporal performance in data collection allowing for monitoring of fast responses to touch stimulation, enabling a truly real time touch sensing. Electromechanical responses of a conductive fabric can be exploited using EIT to create a low cost and large area touch sensing. Such electromechanical properties are often very complex, so to improve the imaging resolution and touch visibility an artificial intelligent (AI) was used in addition to the state of the art spatio-temporal imaging algorithm. This work demonstrates a step towards an integrated seamless skin with large area sensing in dynamical settings, closer to natural human skin’s behaviour. For the first time a dynamical touch sensing are studies by means of a spatio-temporal based electrical impedance tomography (EIT) imaging on a conductive fabric. The experimental results demonstrated the successful results by a combined AI with dynamical EIT imaging results in single and multiple points of touch.

Potential risk to human skin cells from exposure to dicloran photodegradation products in water

Exposure to sunlight and certain pesticides can induce phototoxic responses. Long- and short-term exposure to the photoactivated pesticides can cause a variety of skin diseases. However, assessment of pesticide phototoxicity on human skin is difficult. In the present study, human skin keratinocytes were cultured in several forms: monolayer cell sheet, three-dimensional culture, and keratinocyte-fibroblast co-culture. A common fungicide, dicloran (DC, 2,6‑dichloro‑4‑nitroaniline), was irradiated with simulated sunlight for 2 (DC-PD-2h) and 4 (DC-PD-4h) hours. Dicloran, and two purified intermediate photodegradation products, 2‑chloro‑1,4‑benzoquinone (CBQ) and 1,4‑benzoquinone (BQ), were applied in toxicity tests independently with the keratinocyte culture models. The cell migration, cell differentiation, pro-inflammatory molecule production, and dermal fibroblast cell activation were all measured in the keratinocytes treated with the chemicals described above. These parameters were used as references for dicloran phototoxicity assessment. Among all tested chemicals, the DC-PD-4h and BQ demonstrated elevated toxicities to the keratinocytes compared to dicloran based on our results. The application of DC-PD-4h or BQ significantly delayed the migration of keratinocytes in monolayer cell sheets, inhibited the keratinocyte differentiation, increased the production of pro-inflammatory molecules by 3D keratinocyte culture, and enhanced the ability of 3D cultured keratinocytes in the activation of co-cultured dermal fibroblast cells. In contrast, dicloran, DC-PD-2h, and CBQ showed minimal effects on the keratinocytes in all assays. The results suggested that the four-hour photodegraded dicloran was likely to induce inflammatory skin diseases in the natural human skin. The 1,4‑benzoquinone, which is the predominant degradation product detected following 4 h of irradiation, was the main factor for this response. Photoactivation increased the risk of skin exposed to dicloran in nature. Our models provided an efficient tool in the assessment of toxicity changes in pesticide following normal use practices under typical environmental conditions.

Biomechanical Modeling of Human Skin Tissue Surrogates.

Surrogates, which precisely simulate nonlinear mechanical properties of the human skin at different body sites, would be indispensable for biomechanical testing applications, such as estimating the accurate load response of skin implants and prosthetics to study the biomechanics of static and dynamic loading conditions on the skin, dermatological and sports injuries, and estimating the dynamic load response of lethal and nonlethal ballistics. To date, human skin surrogates have been developed mainly with materials, such as gelatin and polydimethylsiloxane (PDMS), based on assumption of simplified mechanical properties, such as an average elastic modulus (estimated through indentation tests), and Poisson’s ratio. In addition, pigskin and cowhides, which have widely varying mechanical properties, have been used to simulate human skin. In the current work, a novel elastomer-based material system is developed, which precisely mimics the nonlinear stress–stretch behavior, elastic modulus at high and low strains, and fracture strengths of the natural human skin at different body sites. The manufacturing and fabrication process of these skin surrogates are discussed, and mechanical testing results are presented.

NiO@SiO2/PVDF: A Flexible Polymer Nanocomposite for a High Performance Human Body Motion-Based Energy Harvester and Tactile e-Skin Mechanosensor

Advancement in self-powered portable and wearable electronics mostly depends on the realization of an efficient human activity-based energy harvester and electronic skin (e-skin)-mimicking tactile mechanosensing property of natural human skin. A human activity-based energy harvester can supply power to flexible, potable, electronics equipment associated with the human body, whereas a tactile e-skin mechanosensor can precisely detect static and dynamic pressure stimuli. Here, we report development of a NiO@SiO2/PVDF nanocomposite, a facile piezoelectric material possessing superior flexibility that is light in weight and has low cost, which is an excellent choice for the next generation mechanical energy harvester and tactile e-skin sensors. The fabricated piezoelectric nanogenerator (PNG) comprising nanocomposites shows very promising output under application of the biomechanical force on it. PNG15 exhibits high output voltage (53 V), adequate current density (∼0.3 μA/cm2), high power density (685 W/m3), ...

Decontamination of human skin by low-temperature plasma produced by cometary discharge

Abstract Low-temperature plasma produced by DC cometary discharge suppresses bacteria on live human skin of the inner arm side and fingertips. In model experiments, this discharge in open air completely suppressed Escherichia coli within 8 min, whereas Staphylococcus epidermidis was markedly lowered, but not completely eliminated even after 10 min. After inserting an insulated grid and exposure in an enclosed chamber, E. coli was completely suppressed within 2–4 min and S. epidermidis within 10 min. This difference suggests the demand to adapt the European Standard describing the disinfectants and antiseptics test method. Similar results were obtained also for natural human skin bacterial microflora, which was completely quenched after 6–10 min exposure to discharge with the inserted grid acting in an enclosed chamber.

Within touch of artificial skin

Flexible arrays of transducers can now be fabricated with pressure sensitivity and response times approaching those of natural human skin.