Skin Application Research Articles

Piezo-pyrophototronics-based self-powered transparent mechanoreceptor

A mechanoreceptor is a sensor in the human body used to detect signals from the environment, and it induces bodily responses via the brain. We designed a transparent mechanoreceptor using a metal-oxide heterojunction to develop the skin-adopted concept. A highly transparent device (>60%) on PET substrate is obtained using wide bandgap oxide heterostructure. These layers spontaneously provide photovoltaic power (15 μW) to operate the mechanoreceptor without an external power supply system. We show that flexible device provides fast photo response of order of µs, offers solutions ultrafast mechanoreceptor for self-powered skin application. The mechanoreceptor can also operate well above 200 Hz for future ultrafast e-skin. In addition, the photovoltaic mechanoreceptor can be developed on a flexible substrate that is compatible with skin applications such as speedy responses to stimuli (<100 µs). The transparent photovoltaic mechanoreceptor has a self-operational mode and has flexible options in human electronics. • Transparent photovoltaic (TPV) device can generate power for device operation. • Skin-adopted conception of mechanoreceptor is demonstrated with high transparency. • Mechanical sensor is capable of detecting motional variation of body. • Artificial transparent mechanoreceptor detects stimuli at self-operation mode. • Mechanoreceptor has acute and fast responses to stimuli by Piezo-pyrophototronics.

Highly sensitive and wearable bionic piezoelectric sensor for human respiratory monitoring

Flexible piezoelectric sensors hold great promising for applications in electronic skin (E-skin), wearable devices, and biomedical devices. However, it is still challenging to apply flexible piezoelectric sensors to respiratory health monitoring which requires an extremely low detection limit. To address this challenge, a flexible bionic piezoelectric sensor inspired by the lateral line structure of fish is proposed in this study. Benefited from the excellent piezoelectric effect of polyvinylidene fluoride (PVDF) and the bionic structural design, the proposed sensor has a low detection limit of 0.0005 N and can be conformal with a cylindrical surface. In addition, the sensor can accurately sense the pressure at a high sensitivity of 0.24 V N−1 with a fast response time of 4 ms and long-term repeatability of 4000 cycles. Through the design of back-end circuitry, the bionic sensor is capable of accurately monitoring of various respiratory states, such as apnea, coughing, and deep breathing. These results show that our sensor has great potential as a wearable device in the field of respiratory health monitoring, and is also highly inspiring for designing other types of flexible sensors.

Force Sensor Chip With High Lateral Resolution for Artificial Skin and Surgical Applications

The growing interest in artificial skin-based tactile systems requires sufficiently accurate, stretchable, low-power mechanical sensors. In this study, we present a novel capacitive device and an evaluation method capable of retrieving the force vector and determining the position of the loading point on an extended area without the application of a large matrix of individual sensors. With this tool, we can simultaneously increase the extractable information from an extended surface area and reduce the complexity, thereby the power consumption of the system. Thus, an alternative path is opened toward robotic tactile sensing by using a small array of sensors but covering a relatively large receptive field. Even a single sensor can meet the requirements of specific devices—for example, in catheters—to detect tissue hardness, bending, or narrowing of the arteries or veins. Apart from the medical and robotic applications, the flexibility in processing the Flex2Rigid platform enables the mimicry of human fingers or hands with integrated sensors and driving circuits.

Nanometric Systems Containing Ozonated Oil with Potential Activity against Skin Pathogens

ABSTRACT Some antimicrobial substances have unwanted side effects, besides difficulty in crossing the stratum corneum, prompting the need to search for alternative treatments. Ozonated vegetable oils present activity against some fungi and bacteria. This study has aimed to develop and characterize nanoemulsions and polymeric nanocapsules containing 5% ozonated sunflower seed oil for skin application with potential activity against skin pathogens. The formulations were obtained by interfacial deposition of preformed polymer (polymeric nanocapsules) and emulsification followed by Ultra-Turrax® agitation (nanoemulsion). The nanometric systems were evaluated in terms of their organoleptic and physicochemical properties, as well as ozonides presence. The stability of the systems was analyzed by centrifugation (pre-stability) and after 30 days in oven (40 °C) and refrigerator (4 °C) conditions. The antimicrobial activity was determined in vitro using dermatophytes, Candida and Staphylococcus species. Both formulations appeared white and homogeneous, with typical ozonated oil odor. The mean diameters and pH values were, respectively, 139 ± 7.6 nm and 3.2 ± 0.1 for the nanoemulsion and 149 ± 6.1 nm and 3.3 ± 0.2 for the polymeric nanocapsules. Zeta potential was −9 mV (nanoemulsion) and +11 mV (polymeric nanocapsules). The presence of ozonides was confirmed by FT-IR and the nanometric systems were considered stable. Susceptibility tests showed greater potential for the nanometric systems containing ozonated oil against fungi, especially dermatophytes. It was possible to increase the antimicrobial efficacy of the ozonated oil for eighteen of the twenty pathogen isolates tested. Thus, the developed nanometric systems containing ozonated oil may be considered potential treatments for skin infections.

Research on the development of genetically engineered xenogenic porcine skin and its application in the treatment of burn wounds

In the recent years, the shortage of allo-skin sources has resulted in great challenges for salvage of patients with large area severe burns. Although being similar to human skin in construction and function, the clinical application of xenogenic porcine skin in burn wound management is limited due to factors including immuno-rejection, porcine endogenous retroviruses infection, etc. With the development of gene editing technology, especially the emerge of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein-9 system, multiple target genes could be possibly edited at the same time, which will bring broad prospect for the application of xenogenic porcine skin in the treatment of burn wounds. The paper mainly discusses the development, the existed barrier, the strategies of gene modification/editing, and the applications and research of xenogenic porcine skin xenografts in the clinical treatment of burn wound.

Self-Powered Resilient Porous Sensors with Thermoelectric Poly(3,4-ethylenedioxythiophene):Poly(styrenesulfonate) and Carbon Nanotubes for Sensitive Temperature and Pressure Dual-Mode Sensing.

Portable and wearable dual-mode sensors that can simultaneously detect multiple stimuli are essential for emerging artificial intelligence applications, and most efforts are devoted to exploring pressure-sensing devices. It is still challenging to integrate temperature and pressure-sensing functions into one sensor without the requirement for complex decoupling processes. Herein, we develop a self-powered and multifunctional dual-mode sensor by dip-coating melamine sponge with both poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and carboxylated single-walled carbon nanotubes (CNTs). By integrating thermoelectric and conductive PEDOT:PSS/CNT components with the hydrophilic and resilient porous sponge, the resultant sensor is efficient in independently detecting temperature and pressure changes. The temperature and pressure stimuli can be independently converted to voltage and electrical resistance signals on the basis of the Seebeck and piezoresistive effects, respectively. The sensor exhibits a high Seebeck coefficient of 35.9 μV K-1 with a minimum temperature detection limit of 0.4 K and a pressure sensitivity of -3.35% kPa-1 with a minimum pressure detection limit of 4 Pa. Interestingly, the sensor can also be self-powered upon illumination. These multi-functionalities make the sensor a promising tool for applications in electronic skin, soft robots, solar energy conversion, and personal health monitoring.

Human fetal skin derived merkel cells display distinctive characteristics in vitro and in bio-engineered skin substitutes in vivo.

Human skin contains specialized neuroendocrine Merkel cells responsible for fine touch sensation. In the present study, we performed in-depth analysis of Merkel cells in human fetal back skin. We revealed that these Merkel cells expressed cytokeratin 20 (CK20), were positive for the neuroendocrine markers synaptophysin and chromogranin A, and the mechanosensitive ion channel Piezo2. Further, we demonstrated that Merkel cells were present in freshly isolated human fetal epidermal cells in vitro, and in tissue-engineered human dermo-epidermal skin substitutes 4 weeks after transplantation on immune-compromised rats. Merkel cells retained the expression of CK20, synaptophysin, chromogranin A, and Piezo2 after isolation and in culture, and in the skin substitutes after transplantation. Interestingly, we observed that in fetal skin and in skin substitutes, only Merkel cells were positive for CK8, while in culture, also non-Merkel cells showed positivity for CK8. In summary, human fetal Merkel cells showed phenotypical features confirming their cell identity. This findings are of pivotal importance for the future application of fetal tissue-engineered skin in clinics.

Antibacterial and Antifungal Properties of a Novel Antimicrobial Peptide GK-19 and Its Application in Skin and Soft Tissue Infections Induced by MRSA or Candida albicans.

The increasing resistance of human pathogens promotes the development of novel antimicrobial agents. Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-derived peptide, Androctonus amoreuxi Antimicrobial Peptide 1 (AamAP1), has been proved to have broad-spectrum antimicrobial properties. However, AamAP1 can induce hemolysis and shows strong toxicity against mammalian cells. Herein, the antimicrobial activity and mechanism of a novel synthetic antimicrobial peptide, GK-19, derived from AamAP1 and its derivatives, was evaluated. Five bacteria and three fungi were used to evaluate the antimicrobial effects of GK-19 in vitro. Scalded mice models combined with skin and soft tissue infections (SSTIs) were used to evaluate its applicability. The results indicated that GK-19 could not only inhibit Gram-positive and Gram-negative bacterial growth, but also kill fungi by disrupting the microbial cell membrane. Meanwhile, GK-19 showed negligible toxicity to mammalian cells, low hemolytic activity and high stability in plasma. Furthermore, in scalded mice models combined with SSTIs induced by either Methicillin-Resistant Staphylococcus aureus (MRSA) or Candida albicans, GK-19 showed significant antimicrobial and healing effects. Overall, it was demonstrated that GK-19 might be a promising drug candidate in the battle against drug-resistant bacterial and fungal infections.

Interfacial Enhanced 1D–2D Composite toward Mechanically Robust Strain Sensors

AbstractFlexible sensors with the ability to precisely detect the full range of tiny strain (less than 0.1%), small strain (within 1%), and large strain (≈50%) are in significant demand to satisfy the requirements for electronic skin applications. More importantly, the sensor performance is required to be accurate and reliable when operating in some unconstrained environments, such as excessive extension, high bending, torsion, and scratching impact. However, it remains challenging to meet all these requirements simultaneously in a single strain sensor. Herein, an ultrathin composite film composed of reduced oxide (rGO) and carbon tube (CNT) is prepared, and then transferred onto a modified elastomer polydimethylsiloxane surface that forms strong hydrogen bond interaction with the film. The as‐fabricated sensor achieves wide range and high sensitivity (gauge factor (GF) ≈ 105, 160, and 310 in the strain regions of 0–25%, 25–40%, and 40–50%, respectively). More importantly, the proposed strain sensor performs mechanical robustness, low hysteresis, scratch resistance due to the effective improvement of interfacial slipping and delamination. The sensor can be used to monitor human physiological information, including pulse waveforms in a variety of wrist postures and acoustic vibration signal (≈7 kHz).

Cost-Effective, Disposable, Flexible, and Printable MWCNT-Based Wearable Sensor for Human Body Temperature Monitoring

Personalized mobile healthcare integrated with various wearable devices has become a significant area of interest in the present era. In the current research work, a flexible, wearable and disposable paper-based continuous skin temperature monitoring sensor for early medical prognosis and accurate diagnosis of body temperature-related ailments, such as COVID-19, is proposed. Conventional screen-printing and drop-casting techniques were used to fabricate the proposed sensor using MWCNTs as the sensing material and paper as the substrate. The linearity, stability, repeatability and durability of the sensors were tested from 29°C (room temperature) to 60°C. A thin sheet of PET was laminated over the sensor surface to ascertain its stability toward environmental effects and physical movements, and a response time of ~13 s and a recovery time of ~38 s with a sensitivity of −0.0685% °C <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−1</sup> were recorded. The efficacy of the proposed sensor was ascertained by placing it at different body locations on a human subject and comparing it with a standard thermocouple and IR sensor. The sensor even helped to effectively distinguish minimal temperature variations between various regions of the body. Furthermore, the feasibility of the fabricated temperature sensor as a temperature-based tactile sensor for robotics/artificial skin applications and as a noncontact breath monitoring device for use in personalized healthcare monitoring applications was investigated.

Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric care (PID): a study protocol for an exploratory randomised controlled pragmatic trial

IntroductionThe majority of aged long-term care receivers and patients in geriatric acute care are affected by some form of incontinence. These individuals are at risk of developing incontinence-associated dermatitis (IAD),...

Scaffolds in the microbial resistant era: Fabrication, materials, properties and tissue engineering applications.

Due to microbial infections dramatically affect cell survival and increase the risk of implant failure, scaffolds produced with antimicrobial materials are now much more likely to be successful. Multidrug-resistant infections without suitable prevention strategies are increasing at an alarming rate. The ability of cells to organize, develop, differentiate, produce a functioning extracellular matrix (ECM) and create new functional tissue can all be controlled by careful control of the extracellular microenvironment. This review covers the present state of advanced strategies to develop scaffolds with antimicrobial properties for bone, oral tissue, skin, muscle, nerve, trachea, cardiac and other tissue engineering applications. The review focuses on the development of antimicrobial scaffolds against bacteria and fungi using a wide range of materials, including polymers, biopolymers, glass, ceramics and antimicrobials agents such as antibiotics, antiseptics, antimicrobial polymers, peptides, metals, carbon nanomaterials, combinatorial strategies, and includes discussions on the antimicrobial mechanisms involved in these antimicrobial approaches. The toxicological aspects of these advanced scaffolds are also analyzed to ensure future technological transfer to clinics. The main antimicrobial methods of characterizing scaffolds’ antimicrobial and antibiofilm properties are described. The production methods of these porous supports, such as electrospinning, phase separation, gas foaming, the porogen method, polymerization in solution, fiber mesh coating, self-assembly, membrane lamination, freeze drying, 3D printing and bioprinting, among others, are also included in this article. These important advances in antimicrobial materials-based scaffolds for regenerative medicine offer many new promising avenues to the material design and tissue-engineering communities.

Enhanced and sustained transdermal delivery of primaquine from polymeric thermoresponsive hydrogels in combination with Dermarollers®

Primaquine (PMQ) is an effective antimalaria drug with several limitations. We report the combinatorial approach of thermoresponsive hydrogels and Dermarollers® for transdermal delivery of PMQ to overcome these limitations. The hydrogels were prepared using Pluronic F127 (PF127) and F68 (PF68). Specifically, HPMC was added into the formulation to improve the bioadhesive properties. Numerous formulations were prepared, showing that formulation comprising 15 % PF127, 3 % PF68 and 0.4 % HPMC with 1 % PMQ was selected as the optimum formulation. The formulation showed the gelation temperature around 35 °C with bioadhesive strength of 26.43 ± 2.31 dyne.cm2. Importantly, the pH of the formulation was suitable for skin application with the percentage of PMQ recovery of 99.57 ± 3.23 %. Moreover, the hydrogels exhibited free-flow liquid at storage and room temperature and high viscosities in the skin temperature. In vitro release experiments showed that the release of PMQ was sustained for 24 h. Evaluated in extensive ex vivo studies, the treatment with Dermarollers® improved the skin permeation and retention of PMQ for 3 days. In combination with Dermarollers®, the ex vivo permeation of PMQ was sustained and the localization of PMQ in the skin was improved over 72 h.

Flexible Electronic Skin for Monitoring of Grasping State During Robotic Manipulation.

Electronic skin for robotic tactile sensing has been studied extensively over the past years, yet practical applications of electronic skin for the grasping state monitoring during robotic manipulation are still limited. In this study, we present the fabrication and implementation of electronic skin sensor arrays for the detection of unstable grasping. The piezoresistive sensor arrays have the advantages of facile fabrication, fast response, and high reliability. With the tactile data from the sensor array, we propose two quantitative indicators, correlation coefficient and wavelet coefficient, to identify grasping with variable forces and slippage. Those two indicators reflect both time and frequency domain characteristics in the contact forces from the sensor array and can be obtained without large amount of calculation. We demonstrate the utility of this method under various conditions, the results indicate grasping with variable forces, and slippage can be distinguished by this method. The flexible sensor arrays are adopted for tactile sensing on a bionic hand, and the effectiveness of this method in detecting various grasping states has been verified. The electronic skin sensor array and the grasping state monitoring method are promising for applications in robotic dexterous manipulation.

Mathematical Model for Skin Pain Sensation under Local Distributed Mechanical Compression for Electronic Skin Applications.

Skin pain resulting from mechanical compression is one of the most common pains in daily life and the indispensable information for electronic skin to perceive external signals. The external mechanical stimuli are transduced into impulses and transmitted via nerve fiber, and finally, the sensation is perceived via the procession of the nerve system. However, the mathematical mechanism for pain sensation due to mechanical stimuli remains unclear. In this paper, a mathematical model for skin pain sensation under compression is established, in which the Flament solution, the revised Hodgkin–Huxley model, and the mathematical model gate control theory are considered simultaneously. The proposed model includes three parts: a mechanical model of skin compression, a model of transduction, and a model of modulation and perception. It is demonstrated that the pain sensation degree increases with the compression amplitude and decreases with deeper nociceptor location in the skin. With the help of the proposed model, the quantitative relationship between compression pain sensation and external mechanical stimuli is revealed, which has a significant benefit in promoting the design and mechanism research of electronic skin with pain perception function.

A Three-Dimensional Bioprinted Copolymer Scaffold with Biocompatibility and Structural Integrity for Potential Tissue Regeneration Applications.

The present study was to investigate the rheological property, printability, and cell viability of alginate–gelatin composed hydrogels as a potential cell-laden bioink for three-dimensional (3D) bioprinting applications. The 2 g of sodium alginate dissolved in 50 mL of phosphate buffered saline solution was mixed with different concentrations (1% (0.5 g), 2% (1 g), 3% (1.5 g), and 4% (2 g)) of gelatin, denoted as GBH-1, GBH-2, GBH-3, and GBH-4, respectively. The properties of the investigated hydrogels were characterized by contact angle goniometer, rheometer, and bioprinter. In addition, the hydrogel with a proper concentration was adopted as a cell-laden bioink to conduct cell viability testing (before and after bioprinting) using Live/Dead assay and immunofluorescence staining with a human corneal fibroblast cell line. The analytical results indicated that the GBH-2 hydrogel exhibited the lowest loss rate of contact angle (28%) and similar rheological performance as compared with other investigated hydrogels and the control group. Printability results also showed that the average wire diameter of the GBH-2 bioink (0.84 ± 0.02 mm (*** p < 0.001)) post-printing was similar to that of the control group (0.79 ± 0.05 mm). Moreover, a cell scaffold could be fabricated from the GBH-2 bioink and retained its shape integrity for 24 h post-printing. For bioprinting evaluation, it demonstrated that the GBH-2 bioink possessed well viability (>70%) of the human corneal fibroblast cell after seven days of printing under an ideal printing parameter combination (0.4 mm of inner diameter needle, 0.8 bar of printing pressure, and 25 °C of printing temperature). Therefore, the present study suggests that the GBH-2 hydrogel could be developed as a potential cell-laden bioink to print a cell scaffold with biocompatibility and structural integrity for soft tissues such as skin, cornea, nerve, and blood vessel regeneration applications.

Synthesis and Characterization of Cyclodextrin-Based Scaffold Incorporating Ciprofloxacin Antibacterial Agent for Skin Infection Prevention

The treatment of skin infections is one of the most challenging conditions in these days. Clinically most health professionals recommend the antibiotics; however, their efficiency is questionable due to their side effects, as well as their drug delivery capabilities. This work focuses on the noninvasive skin application of the Ciprofloxacin HCL (CFx)-loaded β-Cyclodextrin composite to suppress the antibacterial infections. Silk fibroins are used to enhance the mechanical properties, sodium alginate for dressing properties, while citric acid has been used as a linking agent. Combination of these forms a green composite, which is biocompatible and demonstrates better controlled drug-releasing properties. Four composites are made with different ratios of biocomponents. The composites are characterized by different characterization methods including Fourier transform infrared spectroscopy (FTIR) analysis, scanning electron microscopy (SEM), and electron-dispersive X-ray spectroscopy (EDX) to observe the surface and chemical properties of the composite scaffold. The antibacterial effect of the scaffold was observed through the agar diffusion test method. The results demonstrated that higher the ratio of β-Cyclodextrin, the larger will be the inhibition zone while other materials have limited to no effect of inhibition zone. The characterization tests show a successful bonding and loading of the CFx in the composite. Therefore, β-Cyclodextrin-based green composite scaffolds could be a promising candidate for wound dressing applications with low side effects.

Millimeter-wave imaging and near-field spectroscopy for burn wound assessment

Abstract Diagnostic applications for skin in the microwave range have developed significantly in recent years, due the non-invasiveness of these applications and their ability to assess tissue water content. Despite their capabilities, however, there is still no appropriate clinically applicable microwave tool for the assessment of burn wounds. A common practice is the visual inspection and evaluation of burns by the doctor, which is a challenging task even for experienced medical professionals. An incorrect assessment can have far-reaching consequences, such as unnecessary surgery or surgery that is necessary but omitted. In this paper, two different approaches of millimeter-wave burn wound assessment are presented: millimeter-wave imaging and near-field spectroscopy. For imaging, a MIMO sparse array was used to assess ex vivo burns on porcine skin in the frequency range of 70–80 GHz. With a resonant millimeter-wave near-field probe, reflective spectroscopy at individual sites of an ex vivo burn on porcine skin in the frequency range of 75–110 GHz was performed. The results showed individual advantages and drawbacks for both approaches, with surprising benefits of the spectroscopic method. Nevertheless, both approaches were shown to be suitable for clinical usage in diagnosing burns.

Magnetic Self-Assembled Pearl Necklace-like Microstructure for Improving the Performance of a Flexible Strain Sensor

Flexible strain sensors have important applications in wearable devices, electronic skin, robotics, and virtual reality. However, simple and effective methods to adjust the sensing performance for various applications are still the key to their commercialization. Here, a flexible strain sensor with a magnetic self-assembled pearl necklace-like microstructure is proposed, named PNS-C, which effectively improves its strain sensing performance by utilizing the curing magnetic induction intensity to adjust the arrangement of nanoparticles and multiwalled carbon nanotubes. It exhibited high sensitivity (GF = 361.02, 125–150% strain), nearly 40.16 times that of the corresponding randomly distributed structural composites, fast response (loading delay time was 132 ms), and high durability (1050 cycles). The sensing properties of PNS-C enable wearable health monitoring including facial micro-motion and knee movements. Finally, a manipulator grasping motion detection system is designed to demonstrate the potential practical value of the sensor in the field of robot control.

Wearable nanofibrous tactile sensors with fast response and wireless communication

Flexible tactile sensors with high sensitivity and superior stability have captured considerable research interests recently owing to their promising applications in electronic skin and human–machine interfaces. Herein, a hybrid nanofibrous tactile sensor is developed through the co-electrospinning of TPU/PAN/F127 (TPF) nanofibers and subsequent wrapping of mono-layered Ti3C2Tx flakes. It is proved that the blending of PAN and F127 can significantly improve the fiber uniformity and the interfacial interaction between the fibrous matrix and MXene, leading to the stable and uniform incorporation of the highly conductive Ti3C2Tx flakes. Obtained flexible MXene/TPU/PAN/F127 (MTPF) nanofibrous membrane with interconnected 3D conducting networks manifests a high sensitivity (0.2082 kPa−1), a wide working range (0–160 kPa), rapid response/recovery times (60 ms/120 ms), and long-term durability (8000 cycles) when utilized as an on-skin tactile sensor, which is also assembled into a wearable wireless sensor for the accurate and real-time detection of various human activity signals, evidencing its great potential in high-performance wearable sensory electronics.