Human Skin Research Articles

High-yield, plant-based production of an antimicrobial peptide with potent activity in a mouse model.

Plants offer a promising chassis for the large-scale, cost-effective production of diverse therapeutics, including antimicrobial peptides (AMPs). However, key advances will reduce production costs, including simplifying the downstream processing and purification steps. Here, using Nicotiana benthamiana plants, we present an improved modular design that enables AMPs to be secreted via the endomembrane system and sequestered in an extracellular compartment, the apoplast. Additionally, we translationally fused an AMP to a mutated small ubiquitin-like modifier sequence, thereby enhancing peptide yield and solubilizing the peptide with minimal aggregation and reduced occurrence of necrotic lesions in the plant. This strategy resulted in substantial peptide accumulation, reaching around 2.9 mg AMP per 20 g fresh weight of leaf tissue. Furthermore, the purified AMP demonstrated low collateral toxicity in primary human skin cells, killed pathogenic bacteria by permeabilizing the membrane and exhibited anti-infective efficacy in a preclinical mouse (Mus musculus) model system, reducing bacterial loads by up to three orders of magnitude. A base-case techno-economic analysis demonstrated the economic advantages and scalability of our plant-based platform. We envision that our work can establish plants as efficient bioreactors for producing preclinical-grade AMPs at a commercial scale, with the potential for clinical applications.

Behavioral biometric optical tactile sensor for instantaneous decoupling of dynamic touch signals in real time

Decoupling dynamic touch signals in the optical tactile sensors is highly desired for behavioral tactile applications yet challenging because typical optical sensors mostly measure only static normal force and use imprecise multi-image averaging for dynamic force sensing. Here, we report a highly sensitive upconversion nanocrystals-based behavioral biometric optical tactile sensor that instantaneously and quantitatively decomposes dynamic touch signals into individual components of vertical normal and lateral shear force from a single image in real-time. By mimicking the sensory architecture of human skin, the unique luminescence signal obtained is axisymmetric for static normal forces and non-axisymmetric for dynamic shear forces. Our sensor demonstrates high spatio-temporal screening of small objects and recognizes fingerprints for authentication with high spatial-temporal resolution. Using a dynamic force discrimination machine learning framework, we realized a Braille-to-Speech translation system and a next-generation dynamic biometric recognition system for handwriting.

Environmental fluoxetine promotes skin cell proliferation and wound healing

This study investigates the effects of environmentally-relevant concentrations of fluoxetine (FLX, commercial name: Prozac) on wound healing. Pollution of water systems with pharmaceutical and personal care products, including antidepressants such as FLX and other selective serotonin reuptake inhibitors, is a growing environmental concern. Environmentally-relevant FLX concentrations are known to impact physiological functions and behaviour of aquatic animals, however, the effects of exposure on humans are currently unknown. Using a combination of human skin biopsies and a human keratinocyte cell line, we show that exposure to environmental FLX promotes wound closure. We show dose-dependent increases in wound closure with FLX concentrations from 125 ng/l. Using several –omics and pharmaceutical approaches, we demonstrate that the mechanisms underlying enhanced wound closure are increased cell proliferation and serotonin signalling. Transcriptomic analysis revealed 350 differentially expressed genes after exposure. Downregulated genes were enriched in pathways related to mitochondrial function and metabolism, while upregulated genes were associated with cell proliferation and tissue morphogenesis. Kinase profiling showed altered phosphorylation of kinases linked to the MAPK pathway. Consistent with this, phosphoproteomic analyses identified 235 differentially phosphorylated proteins after exposure, with enriched GO terms related to cell cycle, division, and protein biosynthesis. Treatment of skin biopsies and keratinocytes with ketanserin, a serotonin receptor antagonist, reversed the increase in wound closure observed upon exposure. These findings collectively show that exposure to environmental FLX promotes wound healing through modulating serotonin signalling, gene expression and protein phosphorylation, leading to enhanced cell proliferation. Our results justify a transition from the study of behavioural effects of environmental FLX in aquatic animals to the investigation of effects of exposure on wound healing in aquatic and terrestrial animals, including direct impacts on human health.

A novel amphiphilic squalene-based compound with open-chain polyethers reduces malignant melanoma metastasis in-vitro and in-vivo

Squalene (SQ) is a well-known antioxidant and anti-inflammatory agent that provides promising anti-aging and UV-protective roles on human skin. However, its strong hydrophobic nature, accompanied by issues such as poor solubility and limited tissue permeation, has created challenges for scientists to investigate its untapped potential in more complex conditions, including cancer progression. The present study assessed the potent anti-metastatic properties of a newly synthesized amphiphilic ethylene glycol SQ derivative (SQ-diEG) in melanoma, the most fatal skin cancer. In vitro and in vivo experiments have discovered that SQ-diEG may exert its potential on melanoma malignancy through the mitochondria-mediated caspase activation apoptotic signaling pathway. The potent anti-metastatic effect of SQ-diEG was observed in vitro using highly proliferative and aggressive melanoma cells. Administration of SQ-diEG (25 mg/kg) significantly decreased the tumor burden on the lung and inhibited the metastasis-associated proteins and gene markers in B16F10 lung colonization mice model. Furthermore, global gene profiling also revealed a promising role of SQ-diEG in tumor microenvironment. We anticipated that the amphiphilic nature of the SQ compound bearing ethylene glycol oligomers could potentially augment its ability to reach the pathology site, thus enhancing its therapeutic potential in melanoma.

Glucose-Responsive Microneedle Patch with High Insulin Loading Capacity for Prolonged Glycemic Control in Mice and Minipigs.

Transdermal microneedle-mediated glucose-responsive insulin delivery systems can modulate insulin release based on fluctuations in blood glucose levels, thus maintaining normoglycemia effectively in a continuous, convenient, and minimally invasive manner. However, conventional microneedles are limited by the low drug loading capacity, making it challenging to be applied on human skin at a reasonable size for a lasting glucose-controlling effect, thus hindering their clinical translation. Here, we design a microneedle patch with a solid insulin powder core to achieve a high loading capacity of insulin (>70 wt %) as well as a glucose-sensitive polymeric shell to realize glucose-responsive insulin release. Once exposed to hyperglycemia, the formation of negatively charged glucose-boronate complexes increases the charge density of the shell matrix, leading to swelling of the shell and accelerating insulin release from the core. We have demonstrated that this glucose-responsive microneedle patch could achieve long-term regulation of blood glucose levels in both type 1 diabetic mice and minipigs (up to 48 h with patches of ∼3.5 cm2 for minipigs >25 kg).

Identification of a new human senescent skin cell marker ribonucleoside-diphosphate reductase subunit M2 B.

In skin aging, it has been hypothesized that aging fibroblasts accumulate within the epidermal basal layer, dermis, and subcutaneous fat, causing abnormal tissue remodeling and extracellular matrix dysfunction, thereby inducing an aging-related secretory phenotype (SASP). A new treatment for skin aging involves the specific elimination of senescent skin cells, especially fibroblasts within the dermis and keratinocytes in the basal layer. This requires the identification of specific protein markers of senescent cells, such as ribonucleoside-diphosphate reductase subunit M2 B (RRM2B), which is upregulated in various malignancies in response to DNA stress damage. However, the behavior and role of RRM2B in skin aging remain unclear. Therefore, we examined whether RRM2B functions as a senescence marker using a human dermal fibroblast model of aging. In a model of cellular senescence induced by replicative aging and exposure to ionizing radiation or UVB, RRM2B was upregulated at the gene and protein levels. This was correlated with decreased uptake of the senescence-associated β-galactosidase activity and proliferation marker bromodeoxyuridine. RRM2B upregulation was concurrent with the increased expression of SASP factor genes. Furthermore, using fluorescence flow cytometry, RRM2B-positive cells were recovered more frequently in the aging cell population. In aging human skin, RRM2B was also found to be more abundant in the dermis and epidermal basal layer than other proteins. Therefore, RRM2B may serve as a clinical marker to identify senescent skin cells.

The effect of degeneration of elastic fibres on loss of elasticity and wrinkle formation.

Skin elasticity, which is vital for a youthful appearance, depends on the elastic fibres in the dermis. However, these fibres deteriorate with ageing, resulting in wrinkles and sagging. Changes that occur in the elastic fibres in living human skin and the relationship between elastic fibres and the state of the skin surface remain unclear. Therefore, it is necessary to verify the relationship between elastic fibres and skin elasticity. In this study, we investigated the association of the elastic fibre structure with skin elasticity and stratum corneum protein content in living human skin. Thirty-five female volunteers aged 25-66 years were included in this study. Elastic fibres were observed using a multiphoton scanning laser biomicroscope. Skin elasticity was measured using a Cutometer, and stratum corneum proteins (Heat-shock protein 27 [HSP27] and galectin-7 [Gal-7]) in tape-stripped samples were analysed using an enzyme-linked immunosorbent assay. Elastic fibres exhibited increased curvature and thickness with increased age, with fragmentation observed in women aged >60 years. Elastin scores, which reflect thinness and curvature, were negatively correlated with age, whereas they were positively correlated with R7 elasticity (recovery ability). In individuals aged 20-30 years, higher levels of inflammatory markers (HSP27 and Gal-7) correlated with lower elastin scores; however, this trend was not observed in older participants. Elastic fibre deterioration worsened after 40 years of age, and this effect correlated with reduced skin recovery and increased wrinkles. In younger individuals, inflammatory markers affected elastic fibres. These findings can guide anti-ageing strategies that focus on elastic fibre preservation and inflammation control.

OneTip: A Soft Tactile Interface for 6-D Fingertip Pose Acquisition in Human-Computer Interaction

Advances in display technology have created the need for more efficient and natural multi-degree-of-freedom interaction devices. The movement of a single fingertip has six degrees of freedom (DOFs), but traditional rigid touchscreens usually sense only 2-D information. This article proposes a new deformable tactile interface, OneTip, for single-fingertip human-computer interaction with 6 DOFs. It is manufactured based on the principle of vision-based tactile sensing using virtual stereoscopic cameras, and its size is about twice that of a thumb. The contact surface of OneTip has a specially designed structure and material to mimic the sensitivity and softness of human skin. Also, OneTip employs a new sensing method to address the problem of soft fingertip pose estimation (measuring relative change only) with incipient slip effects. Experiments show that OneTip has good 6-D pose estimation accuracy, with root mean square errors (RMSE) of translation and rotation not exceeding 0.1mm and 2.6°, respectively, within the linear interval (x and y: −1.2 to 1.2mm; z: 0 to 3mm; yaw: −15 to 15deg; pitch and roll: −40 to 40deg). Experiments were also conducted to explore the application of OneTip in typical virtual manipulation tasks and the possibility of combining it with other interaction devices.

Toward an AI Era: Advances in Electronic Skins.

Electronic skins (e-skins) have seen intense research and rapid development in the past two decades. To mimic the capabilities of human skin, a multitude of flexible/stretchable sensors that detect physiological and environmental signals have been designed and integrated into functional systems. Recently, researchers have increasingly deployed machine learning and other artificial intelligence (AI) technologies to mimic the human neural system for the processing and analysis of sensory data collected by e-skins. Integrating AI has the potential to enable advanced applications in robotics, healthcare, and human-machine interfaces but also presents challenges such as data diversity and AI model robustness. In this review, we first summarize the functions and features of e-skins, followed by feature extraction of sensory data and different AI models. Next, we discuss the utilization of AI in the design of e-skin sensors and address the key topic of AI implementation in data processing and analysis of e-skins to accomplish a range of different tasks. Subsequently, we explore hardware-layer in-skin intelligence before concluding with an analysis of the challenges and opportunities in the various aspects of AI-enabled e-skins.

Restoring vancomycin activity against resistant Enterococcus faecalis using a transcription factor decoy as a vanA operon-inhibitor.

Vancomycin-resistant enterococci (VRE) represent a public health threat due to the few available treatments. Such alarm has triggered worldwide initiatives to develop effective antimicrobial compounds and novel delivery and therapeutic strategies. vanA operon is responsible for most cases of acquired vancomycin resistance in enterococci. Development of a transcription factor decoy (TFD) system as a vanA gene transcription-inhibitor. Vancomycin MIC was determined in the presence of TFD-lipoplexes. Additionally, the effect of TFD-lipoplexes on the expression level of the vanA gene and the growth pattern of E. faecalis was evaluated. The haemolytic activity of the developed TFD-lipoplexes and their cytotoxicity were examined. TFD-lipoplexes efficiency in treating vancomycin-resistant E. faecalis (VREF) infection was tested in vivo using a systemic mice infection model. A reduction in vancomycin MIC against VRE from 256 mg/L (resistant) to 16 mg/L (intermediate susceptible), in the presence of TFD-lipoplexes, was recorded. The developed TFD-lipoplexes lacked any effect on E. faecalis growth and significantly reduced the transcription level of the vanA gene by about 3-fold. In an initial evaluation of the safety of TFD-lipoplexes, they were found not to be overtly haemolytic to human blood or cytotoxic to human skin fibroblast cells. The co-administration of TFD-lipoplexes and vancomycin efficiently eradicated VREF infection in vivo. The developed TFD-lipoplexes successfully restored vancomycin activity against VREF. They offer a safe effective unconventional therapy against this stubborn organism and present a revolution in gene therapy that can be applied to other resistance-encoding genes in various organisms.

Culture dependent and independent approaches reveal the role of specific bacteria in human skin aging

AbstractSkin aging is a dynamic process involving a spectrum of phenotypic changes, making it an attractive model for studying microbiome‐phenotype interactions. Therefore, 822 facial microbial samples and 14 skin phenotypes from corresponding areas were assessed in a Chinese cohort. Porphyrins and the chronological age exhibited the most significant microbial variability. We further profiled the dynamics of the skin microbiome associated with age and aging phenotypes. Using a multiple linear regression model, we predicted premature/delayed aging‐related microbial species, mainly Moraxella osloensis and Cutibacterium acnes. We also validated the biological functions of the host‐microbe interactions in vitro. Moraxella osloensis isolated from healthy skin regulates collagen metabolism and extracellular matrix assembly, and promotes cell senescence in human keratinocytes and fibroblasts, making it potentially applicable in the development of antiaging interventions.

High Spatiotemporal Resolution Biomimetic Thermoreceptors Realizing by Jointless p‐n Integration Thermoelectric Composites

AbstractHuman body temperature is a critical physiological indicator, reflecting metabolism and temperature regulation. Biomimetic temperature sensors with high temporal and spatial resolution are highly desired to emulate human skin's temperature perception capabilities. Here, a selective filtration method is proposed to fabricate a jointless p‐n thermoelectric module, integrating p‐type and n‐type materials with minimal interfacial barriers. The structure enables rapid response, minimal signal variation, and a robust linear relationship between open circuit voltage and temperature difference, making it suitable as a biomimetic thermoreceptor for enhancing humanoid robots with intelligent sensing capabilities. A smart thermoelectric sensing system with a high temporal and spatial resolution is developed using with jointless p‐n module as the sensing element. In temporal thermal sensing, the sensing system can timely and effectively identify the heat source, with a fast response time of <0.1 s. In addition, in spatial thermal sensing, the system reliably detects thermal stimuli within discrete regions of each measuring area of <1 × 1 cm2. This study provides an effective strategy for temperature sensors in thermoelectric sensing and biomimetic thermoreceptor applications.

Native valve endocarditis caused by Corynebacterium striatum without underlying structural heart disease or indwelling cardiovascular medical devices: a case report

BackgroundCorynebacterium striatum (C. striatum) is a gram-positive, anaerobic bacillus found both environmentally and in human skin and nasal mucosa flora. It is reportedly the etiologic agent of community-acquired and nosocomial diseases and is significantly associated with bacteremia and medical endovascular devices. This is the rare case of mitral valve native valve endocarditis (NVE) caused by C. striatum occurring in a young adult without underlying structural heart disease or indwelling cardiovascular medical devices successfully treated with multidisciplinary therapy.Case presentationThe patient was a 28-year-old female with no medical history. She was transferred our hospital due to sudden onset of vertigo and vomit. A computed tomography on day 2 revealed the hydrocephalus due to the cerebellar infarction, and she underwent posterior fossa decompression for cerebellar infarction. An angiography on day 8 revealed a left vertebral artery dissection, which was suspected be the etiology. Afterwards, a sudden fever of 39 degrees developed on day 38. She was diagnosed with aspiration pneumonia and treated with ampicillin/sulbactam but was still febrile at the time of transfer for rehabilitation. Treatment continued with levofloxacin, the patient had no fever decline, and she was readmitted to our hospital. Readmission blood cultures (3/3 sets) revealed C. striatum, and an echocardiogram revealed an 11 mm long mitral valve vegetation, leading to NVE diagnosis. On the sixth illness day, cardiac failure symptoms manifested. Echocardiography revealed mitral valve rupture. She was transferred again on the 11th day of illness, during which time her mitral valve was replaced. C. striatum was detected in the vegetation. Following surgery, she returned to our hospital, and vancomycin administration continued. The patient was discharged after 31 total days of postoperative antimicrobial therapy. The patient experienced no exacerbations thereafter.ConclusionsWe report the rare case of C. striatum mitral valve NVE in a young adult without structural heart disease or indwelling cardiovascular devices.Clinical trial numberNot applicable.

MSC Exosomes Containing Valproic Acid Promote Wound Healing by Modulating Inflammation and Angiogenesis.

Chronic wounds that are difficult to heal pose a major challenge for clinicians and researchers. Currently, common treatment methods focus on isolating the wound from the outside world, relying on the tissue at the wound site to grow and heal unaided. Umbilical cord mesenchymal stem cell (MSC) exosomes can promote wound healing by enhancing new blood vessel growth at the wound site. Valproic acid (VPA) reduces the inflammatory response and acts on macrophages to accelerate wound closure. In this study, VPA was loaded into umbilical cord MSC exosomes to form a drug carrier exosome (VPA-EXO) with the aim of investigating the effect of VPA-EXO on wound healing. This study first isolated and obtained umbilical cord MSC exosomes, then added VPA to the exosomes and explored the ability of VPA-EXO to promote the proliferation and migration of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs), as well as the ability to promote the angiogenesis of HUVECs, by using scratch, Transwell, and angiogenesis assays. An in vitro cell model was established and treated with VPA-EXO, and the expression levels of inflammation and pro-angiogenesis-related proteins and genes were examined using Western blot and qRT-PCR. The therapeutic effect of VPA-EXO on promoting wound healing in a whole skin wound model was investigated using image analysis of the wound site, H&E staining, and immunohistochemical staining experiments in a mouse wound model. The in vitro model showed that VPA-EXO effectively promoted the proliferation and migration of human skin fibroblast cells and human umbilical vein endothelial cells; significantly inhibited the expression of MMP-9, IL-1β, IL-8, TNF-α, and PG-E2; and promoted the expression of vascular endothelial growth factors. In the mouse wound model, VPA-EXO reduced inflammation at the wound site, accelerated wound healing, and significantly increased the collagen content of tissue at the wound site. As a complex with dual efficacy in simultaneously promoting tissue regeneration and inhibiting inflammation, VPA-EXO has potential applications in tissue wound healing and vascular regeneration. In future studies, we will further investigate the mechanism of action and application scenarios of drug-loaded exosome complexes in different types of wound healing and vascular regeneration.

Lignin-induced rapid polymerization of asymmetrical adhesion Janus gel for strain sensor

Functional hydrogel sensors have shown explosive growth in the health and medical fields. However, the uniform adhesion and the complicated polymerization process of hydrogels seriously hinder their further development. Herein, inspired by the layered structure of human skin, we prepare a Janus gel using in-situ polymerization. Based on the lignin-Fe3+ dual catalytic system, the rapid polymerization of the gel was achieved at room temperature. By tailoring the mass ratio of lignin and Fe3+ in the precursor, the adhesion of the upper and bottom layers can be easily adjusted. In addition, hydrophobic association is introduced into the upper layer to improve the gel's mechanical properties. The obtained asymmetric bilayer gel has a significant difference in adhesion (7 times), and exhibits excellent mechanical properties in the elongation at break (1437 %) and the breaking strength (463.2 kPa). Moreover, the bilayer gel also has good freezing and UV resistance. We use the bilayer gel as a wearable strain sensor, which shows a wide strain detection range of 0–800 % (maximum gauge factor = 5.3). The proposed simple strategy avoids UV irradiation and heating processes, which provides a new idea for the rapid polymerization of multifunctional Janus hydrogels with adjustable performances.

Facile One-Pot Preparation of Polypyrrole-Incorporated Conductive Hydrogels for Human Motion Sensing.

Conductive hydrogels have been widely used in soft robotics, as well as skin-attached and implantable bioelectronic devices. Among the candidates of conductive fillers, conductive polymers have become popular due to their intrinsic conductivity, high biocompatibility, and mechanical flexibility. However, it is still a challenge to construct conductive polymer-incorporated hydrogels with a good performance using a facile method. Herein, we present a simple method for the one-pot preparation of conductive polymer-incorporated hydrogels involving rapid photocuring of the hydrogel template followed by slow in situ polymerization of pyrrole. Due to the use of a milder oxidant, hydrogen peroxide, for polypyrrole synthesis, the photocuring of the hydrogel template and the growing of polypyrrole proceeded in an orderly manner, making it possible to prepare conductive polymer-incorporated hydrogels in one pot. The preparation process is facile and extensible. Moreover, the obtained hydrogels exhibit a series of properties suitable for biomedical strain sensors, including good conductivity (2.49 mS/cm), high stretchability (>200%), and a low Young's modulus (~30 kPa) that is compatible with human skin.

Effects of low dose skin tissue derived peptides on the function and collagen expression of keloid fibroblasts

This study aims to investigate the effects of the skin tissue derived peptides on proliferation, apoptosis, migration and collagen expressions in keloid fibroblasts. From January 2015 to January 2017, patients with hypertrophic scar who underwent surgical excision in department of plastic surgery of Nanjing maternal and child health hospital were included in this retrospective study. Four peptides were selected from the differential peptides between human hypertrophic scar and normal skin tissue. They were named as peptide deregulated in hypertrophic scar 2-5 (PDHPS2-5). Bioinformatics and functional analysis were performed. A low dose of 10 μmol/L of four peptides were respectively added to the culture medium of human primary keloid fibroblasts for 24 h. Cell counting kit-8 (CCK-8) were used to detect the changes in cell viability. Cell apoptosis was detected by flow cytometry. Cell migration ability was checked by Transwell chamber. The protein expressions of collagen COL1A2 (Collagen type I alpha 2) and the myofibroblast marker gene ACTA2 (Actin alpha 2) were analyzed by Western blot. The results showed that bioinformatics prediction analysis revealed that peptide PDHPS4 has the longest half-life and the highest thermal stability. Compared with the control group, low dose of four peptides had no significant effect on the survival rate and apoptosis of keloid fibroblasts tested by CCK-8 assay and flowcytometry. Transwell analysis showed that one peptides (PDHPS5) can significantly inhibit the cell migration ability (The optical density value in Control is 0.81±0.11, in PDHPS5 is 0.27±0.03, t=8.61, P=0.001). Western blot analysis showed that four peptides (PDHPS2, PDHPS3, PDHPS4, PDHPS5) can significantly inhibit the protein expressions of COL1A2 (The relative protein band intensity in Control is 1.02±0.02, in PDHPS2 is 0.21±0.04, in PDHPS3 is 0.26±0.03, in PDHPS4 is 0.53±0.04, in PDHPS5 is 0.73±0.04, t=31.38, 38.54, 18.88, 11.07 respectively, all P value are less than 0.01). Three peptides (PDHPS2, PDHPS3, PDHPS5) can significantly inhibit the protein expressions of ACTA2 (The relative protein band intensity in Control is 1.02±0.02, in PDHPS2 is 0.64±0.05, in PDHPS3 is 0.77±0.06, in PDHPS5 is 0.47±0.07, t=12.08, 6.38, 14.06 respectively, all P value are less than 0.01). In conclusion, the differentially expressed peptides in human hypertrophic scar tissue can affect the function of keloid fibroblasts and collagen expressions to varying degrees. Among them, two peptides (PDHPS2,PDHPS3) significantly inhibit the protein expressions of COL1A2 and ACTA2. The peptide PDHPS5 has high stability, significantly suppresses cell migration, and reduces the protein expressions of COL1A2 and ACTA2, which may provide a new strategy for scar prevention and treatment.

The Impact of Temperature and the Duration of Freezing on a Hydrogel Used for a 3D-Bioprinted In Vitro Skin Model.

Skin bioprinting has the potential to revolutionize treatment approaches for injuries and surgical procedures, while also providing a valuable platform for assessing and screening cosmetic and pharmaceutical products. This technology offers key advantages, including flexibility and reproducibility, which enable the creation of complex, multilayered scaffolds that closely mimic the intricate microenvironment of native skin tissue. The development of an ideal hydrogel is critical for the successful bioprinting of these scaffolds with incorporated cells. In this study, we used a hydrogel formulation developed in our laboratory to fabricate a 3D-bioprinted skin model. The hydrogel composition was carefully selected based on its high compatibility with human skin cells, incorporating alginate, methyl cellulose, and nanofibrillated cellulose. One of the critical challenges in this process, particularly for its commercialization and large-scale production, is ensuring consistency with minimal batch-to-batch variations. To address this, we explored methods with which to preserve the physicochemical properties of the hydrogels, with a focus on freezing techniques. We validated the pre-frozen hydrogels' printability, rheology, and mechanical and surface properties. Our results revealed that extended freezing times significantly reduced the viscosity of the formulations due to ice crystal formation, leading to a redistribution of the polymer chains. This reduction in viscosity resulted in a more challenging extrusion and increased macro- and microporosity of the hydrogels, as confirmed by nanoCT imaging. The increased porosity led to greater water uptake, swelling, compromised scaffold integrity, and altered degradation kinetics. The insights gained from this study lay a solid foundation for advancing the development of an in vitro skin model with promising applications in preclinical and clinical research.

Robust and Environmentally Friendly MXene-Based Electronic Skin Enabling the Three Essential Functions of Natural Skin: Perception, Protection, and Thermoregulation.

The development of electronic skin (e-skin) emulating the human skin's three essential functions (perception, protection, and thermoregulation) has great potential for human-machine interfaces and intelligent robotics. However, existing studies mainly focus on perception. This study presents a novel, eco-friendly, mechanically robust e-skin replicating human skin's three essential functions. The e-skin is composed of Ti3C2Tx MXene, polypyrrole, and bacterial cellulose nanofibers, where the MXene nanoflakes form the matrix, the bacterial cellulose nanofibers act as the filler, and the polypyrrole serves as a conductive "cross-linker". This design allows customization of the electrical conductivity, microarchitecture, and mechanical properties, integrating sensing (perception), EMI shielding (protection), and thermal management (thermoregulation). The optimal e-skin can effectively sense various motions (including minuscule artery pulses), achieve an EMI shielding efficiency of 63.32 dB at 78 μm thickness, and regulate temperature up to 129 °C in 30 s at 2.4 V, demonstrating its potential for smart robotics in complex scenarios.

Estimating the viscoelastic anisotropy of human skin through high-frequency ultrasound elastography.

The skin is the largest organ of the human body and serves distinct functions in protecting the body. The viscoelastic properties of the skin play a key role in supporting the skin-healing process, also it may be changed due to some skin diseases. In this study, high-frequency ultrasound (HFUS) elastography based on a Lamb wave model was used to noninvasively assess the viscoelastic anisotropy of human skin. Elastic waves were generated through an external vibrator, and the wave propagation velocity was measured through 40MHz ultrafast HFUS imaging. Through the use of a thin-layer gelatin phantom, HFUS elastography was verified to produce highly accurate estimates of elasticity and viscosity. In a human study involving five volunteers, viscoelastic anisotropy was assessed by rotating an ultrasound transducer 360°. An oval-shaped pattern in the elasticity of human forearm skin was identified, indicating the high elastic anisotropy of skin; the average elastic moduli were 24.90±6.63 and 13.64±2.67kPa along and across the collagen fiber orientation, respectively. The average viscosity of all the recruited volunteers was 3.23±0.93Pa·s. Although the examined skin exhibited elastic anisotropy, no evident viscosity anisotropy was observed.