Artificial Skin Research Articles

A digital light processing 3D-printed artificial skin model and full-thickness wound models using silk fibroin bioink.

A three-dimensional (3D) artificial skin model offers diverse platforms for skin transplantation, disease mechanisms, and biomaterial testing for skin tissue. However, implementing physiological complexes such as the neurovascular system with living cells in this stratified structure is extremely difficult. In this study, full-thickness skin models were fabricated from methacrylated silk fibroin (Silk-GMA) and gelatin (Gel-GMA) seeded with keratinocytes, fibroblasts, and vascular endothelial cells representing the epidermis and dermis layers through a digital light processing (DLP) 3D printer. Printability, mechanical properties, and cell viability of the skin hydrogels fabricated with different concentrations of Silk-GMA and Gel-GMA were analyzed to find the optimal concentrations for the 3D printing of the artificial skin model. After the skin model was DLP-3D printed using Gel-GMA 15% + Silk-GMA 5% bioink, cultured, and air-lifted for four weeks, well-proliferated keratinocytes and fibroblasts were observed in histological analysis, and increased expressions of Cytokeratin 13, Phalloidin, and CD31 were noted in immunofluorescence staining. Furthermore, full-thickness skin wound models were 3D-printed to evaluate the wound-healing capabilities of the skin hydrogel. When the epidermal growth factor (EGF) was applied, enhanced wound healing in the epidermis and dermis layer with the proliferation of keratinocytes and fibroblasts was observed. Also, the semi-quantitative reverse transcription-polymerase chain reaction revealed increased expression of Cytokeratin 13, fibroblast growth factor, and CD31 in the EGF-treated group relative to the control group. The DLP 3D-printed artificial skin model was mechanically stable and biocompatible for more than four weeks, demonstrating the potential for application in skin tissue engineering. STATEMENT OF SIGNIFICANCE: A full-thickness artificial skin model was 3D-printed in this study with a digital light processing technique using silk fibroin and gelatin, which mimics the structural and cellular compositions of the human skin. The 3D-printed skin hydrogel ensured the viability of the cells in the skin layers that proliferated well after air-lifting cultivation, shown in the histological analysis and immunofluorescence stainings. Furthermore, full-thickness skin wound models were 3D-printed to evaluate the wound healing capabilities of the skin hydrogel, which demonstrated enhanced wound healing in the epidermis and dermis layer with the application of epidermal growth factor on the wound compared to the control. The bioengineered hydrogel expands the applicability of artificial skin models for skin substitutes, wound models, and drug testing.

Auxetic incisions with alternating slit shapes: a promising technique for enhancing synthetic skin grafts expansion

Split thickness skin grafts are widely used in treating burn injuries. To date, with limited availability of donor skin and minimal expansions offered by conventional skin grafting, it is challenging to cover large and severe burns. In this study, novel synthetic skin grafts with alternating slit (AS) shaped cut patterns were developed and tested to evaluate the expansion potentials offered by auxetic or negative Poisson’s ratio structures in skin grafting. A range of auxetic incision patterns were designed with varying unit cell dimensions, and these were projected onto skin using 3D printing. The mechanical properties and digital image correlation of the created synthetic skin grafts were used to determine stress, effective Poisson’s ratio, meshing ratio (MR), and generated strains for strain loadings of up to 150%. The AS graft simulant with equal slit lengths and low slit spacings exhibited the maximum negative Poisson’s effect, expansion, and Mr Expansions were inversely related with the spacing between slits. The lowest value for the MR and highest stress was observed with high spacing, high horizontal slit length, and low vertical slit length. The expansions were highly sensitive to the applied strain, with low strains exhibiting high auxeticity. Such an extensive experimental investigation of the expansion potentials and stress estimations of skin grafts with varying AS dimensional parameters have not been conducted previously. The findings would be crucial for advancing research on mitigation of large burn injuries using high expansion skin grafts.

Design of Intelligent Protective Composite Material with Stress Rate Sensititivity, Strong Interface Adhesion and Recyclability.

Poly(dimethyl siloxane) (PDMS) elastomers play a significant role in smart materials, actuators, and flexible electronics. However, current PDMS lacks adhesion abilities and intelligent responsive properties, which limit its further application. In this study, the polydimethylsiloxane-ureidopyrimidinone impact hardening polymer (PDMS-UI) composites are manufactured by a dual cross-linking compositing tactic. PDMS, a chemically stable cross-linked network, acts as a framework owing to its excellent mechanical strength, whereas UI, a reversible dynamic physically cross-linked network with quadruple hydrogen bonding, endows the PDMS-UI with excellent self-healing ability (efficiency > 90%) and energy absorption (75.23%). Impressively, owing to multivalent hydrogen bonds, the PDMS-UI exhibits superior adhesion performance: the adhesion strength on various substrates exceed 150kPa and that on the Ferrum substrate reaches 570kPa. These outstanding properties make the PDMS-UI a potential candidate for application in both well-developed fields, such as, wearable protective materials, artificial skin and soft robotics. This article is protected by copyright. All rights reserved.

Large area matrix of MXene/MoSe2 nanohybrid-based flexible piezoresistive pressure sensors for artificial e-skin application

In this study, a MoSe2/Ti3C2Tx nanohybrid-based fabricated flexible physical sensor demonstrates an elevated pressure sensitivity of 14.70 kPa−1 and a highly robust nature withstanding up to ∼2500 cycles. The fabricated pressure sensor's underlying transduction mechanism is elucidated by exploiting the inherent piezoresistive effect and the variation of the Schottky barrier height unveiled by the MoSe2/Ti3C2Tx interface with the assistance of comprehensive band structures that are appreciated by ultraviolet photoelectron spectroscopy. Also, sensors were employed as a 7 × 7 sensor matrix with a large area for tactile sensing and incorporated onto the volunteer hand to determine the artificial skin application.

The antibiotic bead pouch - a useful technique for temporary soft tissue coverage, infection prevention and therapy in trauma surgery.

Soft tissue defects resulting from trauma and musculoskeletal infections can complicate surgical treatment. Appropriate temporary coverage of these defects is essential to achieve the best outcomes for necessary plastic soft tissue defect reconstruction. The antibiotic bead pouch technique is a reasonable surgical approach for managing temporary soft tissue defects following adequate surgical debridement. This technique involves the use of small diameter antibiotic-loaded bone cement beads to fill the dead space created by debridement. By applying antibiotics to the bone cement and covering the beads with an artificial skin graft, high local dosages of antibiotics can be achieved, resulting in the creation of a sterile wound that offers the best starting position for soft tissue and bone defect reconstruction. This narrative review describes the rationale for using this technique, including its advantages and disadvantages, as well as pearls and pitfalls associated with its use in daily practice. In addition, the article provides a comprehensive overview of the literature that has been published since the technique was introduced in surgical practice.

Mechanochromic and Conductive Chiral Nematic Nanostructured Film for Bioinspired Ionic Skins.

Chameleon skin is naturally adaptive and can sense environmental changes and transform sensing into bioelectrical and optical signals by manipulating ion transduction and photonic nanostructures. The increasing interest in mimicking biological skins has considerably promoted the development of advanced photonic materials with an increasing ionic conductivity. Herein, we report the judicious design and fabrication of a bioinspired mechanochromic chiral nematic nanostructured film with good ionic conductivity by infiltrating fluorine-rich ionic liquids (FILs) into a swollen self-assembled cellulose nanocrystal (CNC) film with helical nanoarchitectures. Notably, the introduction of 2-hydroxyethyl acrylate considerably enhances the compatibility of hydrophobic FILs and hydrophilic CNCs. The resulting FIL-CNC nanostructured films exhibited excellent mechanochromism, good ionic conductivity, and outstanding optical/electrical dual-signal sensing performance when used as a bioinspired ionic skin for real-time monitoring of human motions. Owing to the integration of FILs, the underwater stability of the chiral liquid crystal nanostructures of CNCs was significantly enhanced. Notably, underwater contact/contactless sensing modes and encrypted information transmission have been achieved with the FIL-CNC nanostructured film. This study can offer great insights for the advancement of biomimetic multifunctional artificial skins and emerging interactive devices, which can find important applications in wearable iontronics, human-machine interactions, and intelligent robots.

Development of Soft Composite Based Anisotropic Synthetic Skin for Biomechanical Testing

Human skin exhibits highly varying mechanical properties, thickness, hardness, and anisotropy by virtue of changing fiber distributions and orientations, across different body locations. To date, only a few studies have computationally simulated skin anisotropy and no experimental study on synthetic skin exists which can mimic the accurate biomechanical properties of the skin. In this work, unique anisotropic synthetic skin samples were created using an elastic composite-based structure. Both single and multi-layer synthetic skin were fabricated with consistent fiber density and fiber dimensions and varying fiber angles to generate over 100 compositions. The compositions implied stress versus stretch responses in mechanical biaxial testing were compared to those of the skin of a person. Hyperelastic constitutive models were used to characterize the non-uniform test results. The created anisotropic synthetic skin must be essential for reliable Biomechanical investigation of skin free from ethical concerns, undertaking medical training and researching skin pathophysiology and injuries.

Korean Amberjack Skin-Inspired Hyaluronic Acid Bioink for Reconstruction of Human Skin.

Decellularized extracellular matrix (dECM) has been extensively employed as tissue engineering scaffolds because its components can greatly enhance the migration and proliferation of cultivating cells. In this study, we decellularized Korean amberjack skin and incorporated soluble fractions in hyaluronic acid hydrogels with 3D-printed tissue engineering hydrogels to overcome any limitation of animal-derived dECM. The hydrolyzed fish-dECM was mixed with methacrylated hyaluronic acid and chemically crosslinked to 3D-printed fish-dECM hydrogels, where fish-dECM contents affected both printability and injectability of the hydrogels. Swelling ratios and mass erosion of the 3D-printed hydrogels were dependent on fish-dECM contents, where higher fish-dECM in the hydrogel increased swelling ratios and mass erosion rates. The higher content of fish-dECM considerably enhanced the viability of the incorporated cells in the matrix for 7 days. Artificial human skin was constructed by seeding human dermal fibroblasts and keratinocytes in the 3D-printed hydrogels, and a formation of a bilayered skin was visualized with tissue staining. Thus, we envision that 3D-printed hydrogels containing fish-dECM can be an alternative bioink composed of a non-mammal-derived matrix.

AI-On-Skin: Towards Enabling Fast and Scalable On-body AI Inference for Wearable On-Skin Interfaces

Existing artificial skin interfaces lack on-skin AI compute that can provide fast neural network inference for time-critical applications. In this paper, we propose AI-on-skin - a wearable artificial skin interface integrated with a neural network hardware accelerator that can be reconfigured to run diverse neural network models and applications. AI-on-skin is designed to scale to the entire body, comprising tiny, low-power, accelerators distributed across the body. We built 7 AI-on-Skin application prototypes and our user trials show AI-On-Skin achieving 20X and 50X speedup over off-body inference via Bluetooth and on-body centralized microprocessor based inference approach respectively. We also project the power performance of AI-on-skin with our accelerator fabricated as silicon chips instead of emulated on FPGAs and show 10X further power savings. To the best of our knowledge, AI-on-Skin is the first ever wearable prototype to demonstrate skin interfaces with on-body AI inference.

Crack-Based Sensor with Microstructures for Strain and Pressure Sensing

Recent extensive research on flexible electronics has led to the development of various flexible sensors. In particular, sensors inspired by the slit organs of a spider, which utilize cracks in a metal film to measure strain, have garnered considerable interest. This method exhibited significantly high sensitivity, repeatability, and durability in measuring strain. In this study, a thin-film crack sensor was developed using a microstructure. The results exhibited its ability to simultaneously measure the tensile force and pressure in a thin film, further expanding its applications. Furthermore, the strain and pressure characteristics of the sensor were measured and analyzed using an FEM simulation. The proposed method is expected to contribute to the future development of wearable sensors and artificial electronic skin research.

Optimization of human skin keratinocyte culture protocols using bioactive molecules derived from olive oil

Skin damage due to severe burns can compromise patient life. Current tissue engineering methods allow the generation of human skin substitutes for clinical use. However, this process is time-consuming, as the keratinocytes required to generate artificial skin have a low proliferation rate in culture. In this study, we evaluated the pro-proliferative effects of three natural biomolecules isolated from olive oil: phenolic extract (PE), DL-3,4-dihydroxyphenyl glycol (DHFG), and oleuropein (OLP), on cultured human skin keratinocytes. The results showed that PE and OLP increased the proliferation of immortalized human skin keratinocytes, especially at concentrations of 10 and 5 µg/mL, respectively, without altering cell viability. In contrast, DHFG did not produce a significant improvement in keratinocyte proliferation. In normal human skin keratinocytes obtained from skin biopsies, we found that PE, but not OLP, could increase the number of keratinocyte colonies and the area occupied by these cells. Furthermore, this effect was associated with increased KI-67 and Proliferating cell nuclear antigen (PCNA) gene expression. Thus, we propose that PE positively affects keratinocyte proliferation and could be used in culture protocols to improve bioartificial skin generation by tissue engineering.

3D Bioprinting and Its Role in a Wound Healing Renaissance

Abstract3D printing (3DP) is an accessible platform being increasingly utilized by independent researchers in fields ranging from industrial manufacturing to medicine. 3D bioprinting is a form of 3D printing that makes use of “bioinks,” organic or synthetic polymer formulations that are often laden with cells. The wide range of materials available means that bioinks can be tailored to the types of tissue that they are meant to emulate. Human skin has a complex microenvironment consisting of numerous layers, cell types, growth factors, and molecular signaling pathways. 3D bioprinting's flexibility and ability to create complex, bioactive structures means that it has great potential in creating artificial skin constructs for skin wound regeneration. While the available materials and cell types for 3DP are large, an ideal bioink for printing artificial skin remains yet to be found. This review will cover the various types of 3DP, the bioinks commonly used, the functionalization of printed artificial skin constructs, challenges that arise in the 3D bioprinting of skin, and future directions for the field. The structure of skin and the wound healing process will also be discussed, as sufficient understanding of these subjects is key to the development of therapeutic artificial skin constructs.

Recent Trends in Macromolecule-Based Approaches for Hair Loss Treatment.

Macromolecules are large, complex molecules composed of smaller subunits known as monomers. The four primary categories of macromolecules found in living organisms are carbohydrates, lipids, proteins, and nucleic acids; they also encompass a broad range of natural and synthetic polymers. Recent studies have shown that biologically active macromolecules can help regenerate hair, providing a potential solution for current hair regeneration therapies. This review examines the latest developments in the use of macromolecules for the treatment of hair loss. The fundamental principles of hair follicle (HF) morphogenesis, hair shaft (HS) development, hair cycle regulation, and alopecia have been introduced. Microneedle (MN) and nanoparticle (NP) delivery systems are innovative treatments for hair loss. Additionally, the application of macromolecule-based tissue-engineered scaffolds for the in vitro and in vivo neogenesis of HFs is discussed. Furthermore, we explored a new research direction wherein artificial skin platforms are adopted as a promising screening method for hair loss treatment drugs. Through these multifaceted approaches, we identified promising aspects of macromolecules for future hair loss treatments. This article is protected by copyright. All rights reserved.

Highly foldable and free-standing supercapacitor based on hierarchical and hollow MOF-anchored cellulose acetate carbon nanofibers

Flexible electrode materials have achieved great breakthroughs during the past decades. However, many challenges remain such as how to overcome the frangibility and enhance the flexibility, and advance the high specific capacitance. We fabricated a free-standing, foldable, and conductive cellulose acetate (CA)-based metal-organic framework (MOF) composites by facile electrospinning carbonization and co-precipitation method. The sustainable cellulose derivative provides a flexible matrix, which contains hierarchically porous and ample redox activities. The intermolecular interaction is enhanced for coordination between exposed hydroxyl on deacetylated CA and metal ions, thus reduce the fracture of the CA nanofibers. Importantly, multi-layer heterojunction structure and honeycomb-like MOF nanosheets with reversibly flexible deformation create interlamellar pathways to improve the bending resistance of nanofibers. The controlled Co/Zn ion concentration could effectively modulate spatial distribution of Co/Zn MOF to thus generate different conductive channels. The asymmetric flexible supercapacitor based on Ni/Co LDH@ Co/Zn NC@CDCP-N electrode material gives high specific capacitance (175.2 F g−1 at 1 A g−1) and outstanding energy density (54.8 W h kg−1) at high power density (985.5W kg−1). Our work paves a way to facile fabrication of flexible and free-standing electrode materials for practical flexible energy storage, such as artificial electronic skin and soft wearable electronics.

Goal-Directed Tactile Exploration for Body Model Learning Through Self-Touch on a Humanoid Robot

An early integration of tactile sensing into motor coordination is the norm in animals, but still a challenge for robots. Tactile exploration through touches on the body gives rise to first body models and bootstraps further development such as reaching competence. Reaching to one’s own body requires connections of the tactile and motor space only. Still, the problems of high dimensionality and motor redundancy persist. Through an embodied computational model for the learning of self-touch on a simulated humanoid robot with artificial sensitive skin, we demonstrate that this task can be achieved (i) effectively and (ii) efficiently at scale by employing the computational frameworks for the learning of internal models for reaching: intrinsic motivation and goal babbling. We relate our results to infant studies on spontaneous body exploration as well as reaching to vibrotactile targets on the body. We analyze the reaching configurations of one infant followed weekly between 4 and 18 months of age and derive further requirements for the computational model: accounting for (iii) continuous rather than sporadic touch and (iv) consistent redundancy resolution. Results show the general success of the learning models in the touch domain, but also point out limitations in achieving fully continuous touch.

78‐1: Invited Paper: Tactile Scanner as Neuromorphic Skin for Computer Haptics

In computer haptics, haptic devices provide sensory feedback that simulates physical properties and forces for recreating a feeling of touch when interacting with a virtual object. To generate such a feeling, a tactile sensor is required to collect tactile information similar to what human hand or skin does and then render it to drive a high‐fidelity artificial skin for tactile display. In this work, a flexible tactile scanner with a TFT‐based neuromorphic circuit as sensor interface is proposed to acquire tactile information with bionic characteristics. In order to recognize and classify different materials and textured surfaces, such a neuromorphic signal conversion is of necessity to generate neuromorphic data that can be used for artificial neuron network training and learning. Further, the following labelled bionic tactile information can be utilized to generate a motor‐neuron‐like signal to drive a high‐fidelity bionic neuromorphic skin for tactile display, enabling to generate a touch feeling of a virtual object in Metaverse. Therefore, as the first step, a tactile scanner as neuromorphic skin must be used to acquire tactile data for such a purpose.

Electrospun Nanofiber-Based Bioinspired Artificial Skins for Healthcare Monitoring and Human-Machine Interaction

Artificial skin, also known as bioinspired electronic skin (e-skin), refers to intelligent wearable electronics that imitate the tactile sensory function of human skin and identify the detected changes in external information through different electrical signals. Flexible e-skin can achieve a wide range of functions such as accurate detection and identification of pressure, strain, and temperature, which has greatly extended their application potential in the field of healthcare monitoring and human-machine interaction (HMI). During recent years, the exploration and development of the design, construction, and performance of artificial skin has received extensive attention from researchers. With the advantages of high permeability, great ratio surface of area, and easy functional modification, electrospun nanofibers are suitable for the construction of electronic skin and further demonstrate broad application prospects in the fields of medical monitoring and HMI. Therefore, the critical review is provided to comprehensively summarize the recent advances in substrate materials, optimized fabrication techniques, response mechanisms, and related applications of the flexible electrospun nanofiber-based bio-inspired artificial skin. Finally, some current challenges and future prospects are outlined and discussed, and we hope that this review will help researchers to better understand the whole field and take it to the next level.

Amorphous biomineral-reinforced hydrogels with dramatically enhanced toughness for strain sensing

Ionic conductive hydrogels are promising candidates for flexible wearable strain sensors and artificial skin. However, achieving high mechanical and sensing performance concurrently remains challenging. Herein, a novel biomineral-reinforced hydrogel composed of polyacrylamide (PAM) and highly stable amorphous calcium carbonate (ACC) is reported. Benefiting from the dual ionic doping strategy (Mg2+ and PO43−), ACC nanoparticles in hybrid hydrogels show a super stable amorphous nature. The resulting mineral hydrogel displays a high stretchability (>1150% strain), a dramatically enhanced fracture toughness (9.57±1.28 vs. 0.91±0.12 kJ m−2), and a desirable linear strain sensitivity. Moreover, the novel mineral hydrogel exhibits high biocompatibility and flame retardance, making it an appealing candidate for wearable device applications.

3D Printing of Multifunctional Conductive Polymer Composite Hydrogels

AbstractFunctional conductive hydrogels are widely used in various application scenarios, such as artificial skin, cell scaffolds, and implantable bioelectronics. However, their novel designs and technological innovations are severely hampered by traditional manufacturing approaches. Direct ink writing (DIW) is considered a viable industrial‐production 3D‐printing technology for the custom production of hydrogels according to the intended applications. Unfortunately, creating functional conductive hydrogels by DIW has long been plagued by complicated ink formulation and printing processes. In this study, a highly 3D printable poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS)‐based ink made from fully commercially accessible raw materials is demonstrated. It is shown that complex structures can be directly printed with this ink and then precisely converted into high‐performance hydrogels via a post‐printing freeze–thawing treatment. The 3D‐printed hydrogel exhibits high electrical conductivity of ≈2000 S m−1, outstanding elasticity, high stability and durability in water, electromagnetic interference shielding, and sensing capabilities. Moreover, the hydrogel is biocompatible, showing great potential for implantable and tissue engineering applications. With significant advantages, the fabrication strategy is expected to open up a new route to create multifunctional hydrogels with custom features, and can bring new opportunities to broaden the applications of hydrogel materials.

A Comprehensive Review: Interaction of Appearance and Behavior, Artificial Skin, and Humanoid Robot

The development of robotics is undeniable in recent years. Many developing contries face the growth of the elderly population, it is the premise and impetus for the development of research on humanoid robots to serve humans. Many studies on various aspects of robotics are carried out in different parts of the world. Many novel methods were introduced for the design of the robot’s external appearance, internal mechanisms, and gestures. Recent research on humanoid robots is designed to appear to be copies of the anthropometric indicators of real people, which may affect the security of other people’s identities. Besides, these robots cause a feeling of horror in the user if their appearance is in the position of the uncanny valley. Therefore, these designs need to be carefully considered before fabrication. Artificial skin is studied for various purposes such as ensuring collision safety for industrial users and helping robots to perceive basic tactile sensations. This review consists of the recent literature on the interaction of appearance and behavior of robot interaction, artificial skin, and especially humanoid robots, including appearance, such as android and Geminoid robots. This work can provide a reference for humanoid robot research, including uncanny valley hypotheses, artificial skin, and humanoid robots.