Using Artificial Skin Devices as Skin Replacements: Insights into Superficial Treatment.

Artificial skin devices are able to mimic the flexibility and sensory perception abilities of the skin. They have thus garnered attention in the biomedical field as potential skin replacements. This Review delves into issues pertaining to these skin-deep devices. It first elaborates on the roles that these devices have to fulfill as skin replacements, and identify strategies that are used to achieve such functionality. Following which, a comparison is done between the current state of these skin-deep devices and that of natural skin. Finally, an outlook on artificial skin devices is presented, which discusses how complementary technologies can create skin enhancements, and what challenges face such devices.

[1]  Xiaoyang Long,et al.  Magnetogenetics: remote non-invasive magnetic activation of neuronal activity with a magnetoreceptor , 2015, Science bulletin.

[2]  David C. Martin,et al.  Electrochemical polymerization of conducting polymers in living neural tissue , 2007, Journal of neural engineering.

[3]  Michel Destrade,et al.  Characterization of the anisotropic mechanical properties of excised human skin. , 2013, Journal of the mechanical behavior of biomedical materials.

[4]  Justin A. Blanco,et al.  Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. , 2010, Nature materials.

[5]  J W Swanson,et al.  The effect of implantation on the physical properties of silicone rubber. , 1974, Journal of biomedical materials research.

[6]  A. Evangelou,et al.  The effect of pulsed electromagnetic fields on secondary skin wound healing: An experimental study , 2007, Bioelectromagnetics.

[7]  Xuanhe Zhao,et al.  Skin-inspired hydrogel–elastomer hybrids with robust interfaces and functional microstructures , 2016, Nature Communications.

[8]  Jung Woo Lee,et al.  Epidermal electronics with advanced capabilities in near-field communication. , 2015, Small.

[9]  Zibiao Li,et al.  Towards the development of polycaprolactone based amphiphilic block copolymers: molecular design, self-assembly and biomedical applications. , 2014, Materials science & engineering. C, Materials for biological applications.

[10]  X. Tao,et al.  Fiber‐Based Wearable Electronics: A Review of Materials, Fabrication, Devices, and Applications , 2014, Advanced materials.

[11]  Guoqiang Chen,et al.  Characterization, biodegradability and blood compatibility of poly[(R)-3-hydroxybutyrate] based poly(ester-urethane)s. , 2009, Journal of biomedical materials research. Part A.

[12]  R. Dauskardt,et al.  An ultra-sensitive resistive pressure sensor based on hollow-sphere microstructure induced elasticity in conducting polymer film , 2014, Nature Communications.

[13]  Kenneth L. Shepard,et al.  Hybrid integrated biological–solid-state system powered with adenosine triphosphate , 2015, Nature Communications.

[14]  S. Bauer,et al.  Biocompatible and Biodegradable Materials for Organic Field‐Effect Transistors , 2010 .

[15]  P. Gallop,et al.  Cross-linking in collagen and elastin. , 1984, Annual review of biochemistry.

[16]  Ling-Zhi Liu,et al.  Responsive nanoporous metals: recoverable modulations on strength and shape by watering , 2016, Nanotechnology.

[17]  M. Cicerone,et al.  Alternating current electric field effects on neural stem cell viability and differentiation , 2010, Biotechnology progress.

[18]  X. Loh,et al.  Water soluble polyhydroxyalkanoates: future materials for therapeutic applications. , 2015, Chemical Society reviews.

[19]  Eric D. Siggia,et al.  A method to recapitulate early embryonic spatial patterning in human embryonic stem cells , 2014, Nature Methods.

[20]  R. Sanjeevi,et al.  Effect of strain rate on the fracture behaviour of skin , 1994, Journal of Biosciences.

[21]  Stijn Billiet,et al.  Chemistry of crosslinking processes for self-healing polymers. , 2013, Macromolecular rapid communications.

[22]  Jun Li,et al.  Control of hyperbranched structure of polycaprolactone/poly(ethylene glycol) polyurethane block copolymers by glycerol and their hydrogels for potential cell delivery. , 2013, The journal of physical chemistry. B.

[23]  Z. Suo,et al.  Highly stretchable and tough hydrogels , 2012, Nature.

[24]  M. Slater,et al.  The building blocks of the full body ownership illusion , 2013, Front. Hum. Neurosci..

[25]  Jung Hyun Han,et al.  Generation of electrical power under human skin by subdermal solar cell arrays for implantable bioelectronic devices. , 2017, Biosensors & bioelectronics.

[26]  Jonathan A. Fan,et al.  Materials and Designs for Wireless Epidermal Sensors of Hydration and Strain , 2014 .

[27]  Takao Someya,et al.  Ultrathin, highly flexible and stretchable PLEDs , 2013, Nature Photonics.

[28]  Christoph Huber,et al.  Successful pacing using a batteryless sunlight-powered pacemaker. , 2014, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[29]  N. Elvassore,et al.  Mechanotransduction through substrates engineering and microfluidic devices , 2016 .

[30]  I. Yannas,et al.  Wound tissue can utilize a polymeric template to synthesize a functional extension of skin. , 1982, Science.

[31]  Wen Yang,et al.  On the tear resistance of skin , 2015, Nature Communications.

[32]  Peter G Shakespeare,et al.  The role of skin substitutes in the treatment of burn injuries. , 2005, Clinics in dermatology.

[33]  D. Stocum.  Repair of Skin by Fibrosis , 2012 .

[34]  Christian Holz,et al.  DuoSkin: rapidly prototyping on-skin user interfaces using skin-friendly materials , 2016, SEMWEB.

[35]  C. Byrne,et al.  Covering the limb – formation of the integument , 2003, Journal of anatomy.

[36]  Chanseok Lee,et al.  Ultrasensitive mechanical crack-based sensor inspired by the spider sensory system , 2014, Nature.

[37]  Vijay A. Singh,et al.  The Pathogenesis of Burn Wound Conversion , 2007 .

[38]  Xian Jun Loh,et al.  Review of Adaptive Programmable Materials and Their Bioapplications. , 2016, ACS applied materials & interfaces.

[39]  A Heller,et al.  Biocompatible, glucose-permeable hydrogel for in situ coating of implantable biosensors. , 1997, Biomaterials.

[40]  Qing Zhou,et al.  Preparation of high strength and optically transparent silicone rubber , 1998 .

[41]  Chiara Daraio,et al.  Biomimetic temperature-sensing layer for artificial skins , 2015, Science Robotics.

[42]  Zibiao Li,et al.  Targeted delivery of Bcl-2 conversion gene by MPEG-PCL-PEI-FA cationic copolymer to combat therapeutic resistant cancer. , 2017, Materials science & engineering. C, Materials for biological applications.

[43]  T. Trung,et al.  Flexible and Stretchable Physical Sensor Integrated Platforms for Wearable Human‐Activity Monitoringand Personal Healthcare , 2016, Advanced materials.

[44]  Daniel R. King,et al.  Energy‐Dissipative Matrices Enable Synergistic Toughening in Fiber Reinforced Soft Composites , 2017 .

[45]  Ilker S. Bayer,et al.  Electronic Skin: Carbon Nanofiber versus Graphene‐Based Stretchable Capacitive Touch Sensors for Artificial Electronic Skin (Adv. Sci. 2/2018) , 2018, Advanced Science.

[46]  Ja Hoon Koo,et al.  Colloidal Synthesis of Uniform‐Sized Molybdenum Disulfide Nanosheets for Wafer‐Scale Flexible Nonvolatile Memory , 2016, Advanced materials.

[47]  C. Lampert.  Chromogenic smart materials , 2004 .

[48]  X. Loh,et al.  Polyhydroxyalkanoates: Chemical Modifications Toward Biomedical Applications , 2014 .

[49]  T. Lewis.  Observations on Some Normal and Injurious Effects of Cold upon the Skin and Underlying Tissues , 1941, British medical journal.

[50]  R. Sarpeshkar,et al.  A Glucose Fuel Cell for Implantable Brain–Machine Interfaces , 2012, PloS one.

[51]  P. Delaney,et al.  View of normal human skin in vivo as observed using fluorescent fiber-optic confocal microscopic imaging. , 2003, The Journal of investigative dermatology.

[52]  Gunnar A. Niklasson,et al.  Progress in chromogenics: New results for electrochromic and thermochromic materials and devices , 2009 .

[53]  D. Narmoneva,et al.  Modulation of cell function by electric field: a high-resolution analysis , 2015, Journal of The Royal Society Interface.

[54]  Zhigang Suo,et al.  Transparent hydrogel with enhanced water retention capacity by introducing highly hydratable salt , 2014 .

[55]  Changhyun Pang,et al.  Recent advances in flexible sensors for wearable and implantable devices , 2013 .

[56]  Jung Woo Lee,et al.  Multifunctional Skin‐Like Electronics for Quantitative, Clinical Monitoring of Cutaneous Wound Healing , 2014, Advanced healthcare materials.

[57]  Joseph Wang,et al.  A wearable chemical–electrophysiological hybrid biosensing system for real-time health and fitness monitoring , 2016, Nature Communications.

[58]  X. Loh,et al.  Dual-responsive hybrid thermoplastic shape memory polyurethane , 2017 .

[59]  Ye Zhou,et al.  Highly Sensitive and Ultrastable Skin Sensors for Biopressure and Bioforce Measurements Based on Hierarchical Microstructures. , 2018, ACS applied materials & interfaces.

[60]  Zhenan Bao,et al.  Tough and Water‐Insensitive Self‐Healing Elastomer for Robust Electronic Skin , 2018, Advanced materials.

[61]  R. Schwartz,et al.  Modern Aspects of Wound Healing: An Update , 2000, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[62]  Rebecca Heath,et al.  Abnormal pigmentation within cutaneous scars: A complication of wound healing , 2012, Indian Journal of Plastic Surgery.

[63]  David C. Martin,et al.  In vivo polymerization of poly(3,4-ethylenedioxythiophene) in the living rat hippocampus does not cause a significant loss of performance in a delayed alternation task , 2014, Journal of neural engineering.

[64]  Nae-Eung Lee,et al.  An All‐Elastomeric Transparent and Stretchable Temperature Sensor for Body‐Attachable Wearable Electronics , 2016, Advanced materials.

[65]  Yan Ma,et al.  Thermally Stable, Biocompatible, and Flexible Organic Field‐Effect Transistors and Their Application in Temperature Sensing Arrays for Artificial Skin , 2015 .

[66]  Zhong Lin Wang,et al.  Recent Progress in Electronic Skin , 2015, Advanced science.

[67]  Wenjun Zou,et al.  Patterned growth of polyaniline nanowire arrays on a flexible substrate for high-performance gas sensing. , 2011, Small.

[68]  P. P. Lele,et al.  The relationship between heat transfer, skin temperature and cutaneous sensibility , 1954, The Journal of physiology.

[69]  M. Millan,et al.  The induction of pain: an integrative review , 1999, Progress in Neurobiology.

[70]  Zibiao Li,et al.  Recent Progress in Using Stereocomplexation for Enhancement of Thermal and Mechanical Property of Polylactide , 2016 .

[71]  G. Fisher,et al.  UV-light-induced signal cascades and skin aging , 2002, Ageing Research Reviews.

[72]  T. Someya,et al.  A large-area wireless power-transmission sheet using printed organic transistors and plastic MEMS switches. , 2007, Nature materials.

[73]  Craig A. Poland,et al.  Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study. , 2008, Nature nanotechnology.

[74]  B. Edin,et al.  Skin strain patterns provide kinaesthetic information to the human central nervous system. , 1995, The Journal of physiology.

[75]  P. Vogt,et al.  Tissue Engineered Skin Substitutes Created by Laser-Assisted Bioprinting Form Skin-Like Structures in the Dorsal Skin Fold Chamber in Mice , 2013, PloS one.

[76]  Christopher S. Chen,et al.  Cells lying on a bed of microneedles: An approach to isolate mechanical force , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[77]  N. Kirby,et al.  Collagen orientation and leather strength for selected mammals. , 2013, Journal of agricultural and food chemistry.

[78]  Ting Wang,et al.  Soft Thermal Sensor with Mechanical Adaptability , 2016, Advanced materials.

[79]  P. Searson,et al.  The Influence of Electric Field and Confinement on Cell Motility , 2013, PloS one.

[80]  M. Milinkovitch,et al.  Photonic crystals cause active colour change in chameleons , 2015, Nature Communications.

[81]  U. Mariani,et al.  WATER AND ELECTROLYTE CONTENT OF NORMAL SKIN, SCARS, AND KELOID , 1971, Plastic and reconstructive surgery.

[82]  S Annaheim,et al.  Materials used to simulate physical properties of human skin , 2016, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[83]  Xian Jun Loh,et al.  PHB‐Based Gels as Delivery Agents of Chemotherapeutics for the Effective Shrinkage of Tumors , 2016, Advanced healthcare materials.

[84]  Ali Khademhosseini,et al.  Advances in engineering hydrogels , 2017, Science.

[85]  N. Elvassore,et al.  Micropatterning topology on soft substrates affects myoblast proliferation and differentiation. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[86]  Zheng‐Hong Luo,et al.  Mussel-inspired V-shaped copolymer coating for intelligent oil/water separation , 2017 .

[87]  M. Lebwohl,et al.  The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey. , 2001, Archives of dermatology.

[88]  I. Park,et al.  Stretchable, Skin‐Mountable, and Wearable Strain Sensors and Their Potential Applications: A Review , 2016 .

[89]  Lin Jia,et al.  Epidermal photonic devices for quantitative imaging of temperature and thermal transport characteristics of the skin , 2014, Nature Communications.

[90]  Xian Huang,et al.  Adaptive optoelectronic camouflage systems with designs inspired by cephalopod skins , 2014, Proceedings of the National Academy of Sciences.

[91]  M. Ueda,et al.  UV-induced skin damage. , 2003, Toxicology.

[92]  M. Soengas,et al.  Artificial skin in perspective: concepts and applications , 2011, Pigment cell & melanoma research.

[93]  Xian Jun Loh,et al.  Control of PLA Stereoisomers-Based Polyurethane Elastomers as Highly Efficient Shape Memory Materials , 2017 .

[94]  François Berthod,et al.  Improvement of nerve regeneration in tissue-engineered skin enriched with schwann cells. , 2009, The Journal of investigative dermatology.

[95]  D. Narmoneva,et al.  Regulation of endothelial MAPK/ERK signalling and capillary morphogenesis by low-amplitude electric field , 2013, Journal of The Royal Society Interface.

[96]  I. Goudarzi,et al.  Pulsed electromagnetic fields accelerate wound healing in the skin of diabetic rats , 2010, Bioelectromagnetics.

[97]  E. Kenawy,et al.  The chemistry and applications of antimicrobial polymers: a state-of-the-art review. , 2007, Biomacromolecules.

[98]  P. Netti,et al.  In vitro activation of the neuro-transduction mechanism in sensitive organotypic human skin model. , 2017, Biomaterials.

[99]  James J. S. Norton,et al.  Materials and Optimized Designs for Human‐Machine Interfaces Via Epidermal Electronics , 2013, Advanced materials.

[100]  Gijsbertus J.M. Krijnen,et al.  Interfacing of differential-capacitive biomimetic hair flow-sensors for optimal sensitivity , 2013 .

[101]  B. Shirinzadeh,et al.  A wearable and highly sensitive pressure sensor with ultrathin gold nanowires , 2014, Nature Communications.

[102]  Warren M Grill,et al.  Implanted neural interfaces: biochallenges and engineered solutions. , 2009, Annual review of biomedical engineering.

[103]  D. Ginty,et al.  The gentle touch receptors of mammalian skin , 2014, Science.

[104]  R. Anderson,et al.  The optics of human skin. , 1981, The Journal of investigative dermatology.

[105]  T. Someya,et al.  A Rubberlike Stretchable Active Matrix Using Elastic Conductors , 2008, Science.

[106]  T. Someya,et al.  Conformable, flexible, large-area networks of pressure and thermal sensors with organic transistor active matrixes. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[107]  Yonggang Huang,et al.  Stretchable and Foldable Silicon Integrated Circuits , 2008, Science.

[108]  Edoardo Mazza,et al.  On the cyclic deformation behavior, fracture properties and cytotoxicity of silicone-based elastomers for biomedical applications , 2017 .

[109]  Joselito M. Razal,et al.  Progress toward robust polymer hydrogels , 2011 .

[110]  K. Wynne,et al.  PDMS–Fluorous Polyoxetane–PDMS Triblock Hybrid Elastomers: Tough and Transparent with Novel Bulk Morphologies , 2012 .

[111]  J Heikenfeld,et al.  The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. , 2015, Biomicrofluidics.

[112]  P. Thompson,et al.  Lowering relative humidity level increases epidermal protein deimination and drives human filaggrin breakdown. , 2017, Journal of dermatological science.

[113]  E Bell,et al.  Living tissue formed in vitro and accepted as skin-equivalent tissue of full thickness. , 1981, Science.

[114]  Yonggang Huang,et al.  Epidermal radio frequency electronics for wireless power transfer , 2016, Microsystems & Nanoengineering.

[115]  Sung-hoon Ahn,et al.  A flexible and highly sensitive strain-gauge sensor using reversible interlocking of nanofibres. , 2012, Nature materials.

[116]  Yan Jin,et al.  Reconstruction of a tissue‐engineered skin containing melanocytes , 2007, Cell biology international.

[117]  Jianping Fu,et al.  Assaying stem cell mechanobiology on microfabricated elastomeric substrates with geometrically modulated rigidity , 2011, Nature Protocols.

[118]  R. Normann,et al.  Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex , 1998, Journal of Neuroscience Methods.

[119]  David C. Martin,et al.  In vivo studies of polypyrrole/peptide coated neural probes. , 2003, Biomaterials.

[120]  Jan Vanfleteren,et al.  Adhesion enhancement by a dielectric barrier discharge of PDMS used for flexible and stretchable electronics , 2007 .

[121]  James M. Anderson,et al.  Foreign body reaction to biomaterials. , 2008, Seminars in immunology.

[122]  Jonathan Reeder,et al.  Three-Dimensional Flexible Electronics Enabled by Shape Memory Polymer Substrates for Responsive Neural Interfaces. , 2012, Macromolecular materials and engineering.

[123]  T. Humphreys,et al.  The Biomechanical Properties of the Skin , 2013, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[124]  Wisniewski,et al.  Methods for reducing biosensor membrane biofouling. , 2000, Colloids and surfaces. B, Biointerfaces.

[125]  Yunjiang Jiang,et al.  Acid-Activated Antimicrobial Random Copolymers: A Mechanism-Guided Design of Antimicrobial Peptide Mimics , 2013 .

[126]  R. Bellamkonda,et al.  Neural Interfaces: from Human Nerves to Electronics , 2014 .

[127]  Zhouyue Lei,et al.  A supramolecular biomimetic skin combining a wide spectrum of mechanical properties and multiple sensory capabilities , 2018, Nature Communications.

[128]  Benjamin C. K. Tee,et al.  Flexible polymer transistors with high pressure sensitivity for application in electronic skin and health monitoring , 2013, Nature Communications.

[129]  A. Mata,et al.  Characterization of Polydimethylsiloxane (PDMS) Properties for Biomedical Micro/Nanosystems , 2005, Biomedical microdevices.

[130]  Boris Murmann,et al.  Skin electronics from scalable fabrication of an intrinsically stretchable transistor array , 2018, Nature.

[131]  Benjamin C. K. Tee,et al.  Skin-like pressure and strain sensors based on transparent elastic films of carbon nanotubes. , 2011, Nature nanotechnology.

[132]  Maria E. Mycielska,et al.  Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease , 2004, Journal of Cell Science.

[133]  Alex Rodriguez,et al.  A wirelessly powered and controlled device for optical neural control of freely-behaving animals , 2011, Journal of neural engineering.

[134]  Sidney José Lima Ribeiro,et al.  Bacterial cellulose membrane as flexible substrate for organic light emitting devices , 2008 .

[135]  H. Cleland,et al.  Bioengineered skin substitutes for the management of burns: a systematic review. , 2007, Burns : journal of the International Society for Burn Injuries.

[136]  Dukhyun Choi,et al.  An Ultrasensitive, Visco‐Poroelastic Artificial Mechanotransducer Skin Inspired by Piezo2 Protein in Mammalian Merkel Cells , 2017, Advanced materials.

[137]  M. Berggren,et al.  Organic electronics for precise delivery of neurotransmitters to modulate mammalian sensory function. , 2009, Nature materials.

[138]  Xian Jun Loh,et al.  Recent development of synthetic nonviral systems for sustained gene delivery. , 2017, Drug discovery today.

[139]  P. Hammond.  Form and Function in Multilayer Assembly: New Applications at the Nanoscale , 2004 .

[140]  Dermot Diamond,et al.  Glucose Sensing for Diabetes Monitoring: Recent Developments , 2017, Sensors.

[141]  Xiaodong Chen,et al.  Flexible Transparent Films Based on Nanocomposite Networks of Polyaniline and Carbon Nanotubes for High-Performance Gas Sensing. , 2015, Small.

[142]  Meifang Zhu,et al.  Highly Conductive, Flexible, and Compressible All‐Graphene Passive Electronic Skin for Sensing Human Touch , 2014, Advanced materials.

[143]  Feng Zhang,et al.  An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology , 2007, Journal of neural engineering.

[144]  Ke-Qin Zhang,et al.  Highly flexible and lightweight organic solar cells on biocompatible silk fibroin. , 2014, ACS applied materials & interfaces.

[145]  Yan Jin,et al.  Functional neovascularization in tissue engineering with porcine acellular dermal matrix and human umbilical vein endothelial cells. , 2011, Tissue engineering. Part C, Methods.

[146]  B. Bean.  The action potential in mammalian central neurons , 2007, Nature Reviews Neuroscience.

[147]  M. Kirkland,et al.  TISSUE COMPATIBILITY OF BIOMATERIALS: BENEFITS AND PROBLEMS OF SKIN BIOINTEGRATION , 2008, ANZ journal of surgery.

[148]  Ellen A. Lumpkin,et al.  Mechanisms of sensory transduction in the skin , 2007, Nature.

[149]  I. Yannas,et al.  Design of an artificial skin. I. Basic design principles. , 1980, Journal of biomedical materials research.

[150]  Rui M. V. Abreu,et al.  1-Aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as VEGFR-2 Tyrosine Kinase Inhibitors: Synthesis, Biological Evaluation, and Molecular Modelling Studies , 2013, BioMed research international.

[151]  Andrew J. Noss,et al.  The use of camera traps for estimating jaguar Panthera onca abundance and density using capture/recapture analysis , 2004, Oryx.

[152]  Guoqiang Chen,et al.  Novel amphiphilic poly(ester‐urethane)s based on poly[(R)‐3‐hydroxyalkanoate]: synthesis, biocompatibility and aggregation in aqueous solution , 2008 .

[153]  F. Berthod,et al.  Nerve regeneration in a collagen-chitosan tissue-engineered skin transplanted on nude mice. , 2003, Biomaterials.

[154]  David Nilsson,et al.  Active Control of Epithelial Cell‐Density Gradients Grown Along the Channel of an Organic Electrochemical Transistor , 2009, Advanced materials.

[155]  J. Xin,et al.  Temperature-responsive nanofibers for controllable oil/water separation , 2015 .

[156]  Xuewen Wang,et al.  Silk‐Molded Flexible, Ultrasensitive, and Highly Stable Electronic Skin for Monitoring Human Physiological Signals , 2014, Advanced materials.

[157]  Xian Jun Loh,et al.  Recent Advances in Shape Memory Soft Materials for Biomedical Applications. , 2016, ACS applied materials & interfaces.

[158]  Zheng Zhang,et al.  Self-powered artificial electronic skin for high-resolution pressure sensing , 2017 .

[159]  J. Brandner,et al.  The skin: an indispensable barrier , 2008, Experimental dermatology.

[160]  J. Szolcsányi.  Forty years in capsaicin research for sensory pharmacology and physiology , 2004, Neuropeptides.

[161]  Y. Rim,et al.  Recent Progress in Materials and Devices toward Printable and Flexible Sensors , 2016, Advanced materials.

[162]  Min Zhao,et al.  Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTEN , 2006, Nature.

[163]  D. Breitkreutz,et al.  Skin Basement Membrane: The Foundation of Epidermal Integrity—BM Functions and Diverse Roles of Bridging Molecules Nidogen and Perlecan , 2013, BioMed research international.

[164]  Kwang-Seok Yun,et al.  All-polymer hair structure with embedded three-dimensional piezoresistive force sensors , 2012 .

[165]  Dino Di Carlo,et al.  Induction of Calcium Influx in Cortical Neural Networks by Nanomagnetic Forces. , 2016, ACS nano.

[166]  Xiaochen Wu,et al.  Biomimetic Hybridization of Kevlar into Silk Fibroin: Nanofibrous Strategy for Improved Mechanic Properties of Flexible Composites and Filtration Membranes. , 2017, ACS nano.

[167]  Soo-Young Kang,et al.  An elastic second skin. , 2016, Nature materials.

[168]  D. Di Carlo,et al.  Magnetic Nanoparticle-Based Mechanical Stimulation for Restoration of Mechano-Sensitive Ion Channel Equilibrium in Neural Networks. , 2017, Nano letters.

[169]  M. Oshima,et al.  Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model , 2016, Science Advances.

[170]  F. Papadimitrakopoulos,et al.  Dexamethasone-loaded poly(lactic-co-glycolic) acid microspheres/poly(vinyl alcohol) hydrogel composite coatings for inflammation control. , 2004, Diabetes technology & therapeutics.

[171]  X. Loh,et al.  Safe and efficient membrane permeabilizing polymers based on PLLA for antibacterial applications , 2016 .

[172]  Joong Tark Han,et al.  Stretchable and Multimodal All Graphene Electronic Skin , 2016, Advanced materials.

[173]  Goangseup Zi,et al.  Stretchable Active Matrix Temperature Sensor Array of Polyaniline Nanofibers for Electronic Skin , 2016, Advanced materials.

[174]  Hyungpil Moon,et al.  Customizable, Flexible Pressure, and Temperature Step Sensors with Human Skinlike Color , 2018, ACS omega.

[175]  Muhammad Akram Karimi,et al.  Paper Skin Multisensory Platform for Simultaneous Environmental Monitoring , 2016 .

[176]  Menghao Wang,et al.  Mussel‐Inspired Adhesive and Conductive Hydrogel with Long‐Lasting Moisture and Extreme Temperature Tolerance , 2018 .

[177]  Federica Chiellini,et al.  Chitosan—A versatile semi-synthetic polymer in biomedical applications , 2011 .

[178]  Rahul Sarpeshkar.  Ultra Low Power Bioelectronics: Energy harvesting and the future of energy , 2010 .

[179]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[180]  Azbel MYa,et al.  Universal biological scaling and mortality , 1994 .

[181]  X. Loh,et al.  Conjugation of poly(ethylene glycol) to poly(lactide)-based polyelectrolytes: An effective method to modulate cytotoxicity in gene delivery. , 2017, Materials science & engineering. C, Materials for biological applications.

[182]  X. Loh,et al.  “Y”-shape armed amphiphilic star-like copolymers: design, synthesis and dual-responsive unimolecular micelle formation for controlled drug delivery , 2017 .

[183]  Nicola Vitiello,et al.  Synthetic and Bio-Artificial Tactile Sensing: A Review , 2013, Sensors.

[184]  M. L. Hernández-Bule,et al.  Electric Stimulation at 448 kHz Promotes Proliferation of Human Mesenchymal Stem Cells , 2014, Cellular Physiology and Biochemistry.

[185]  H. Athenstaedt,et al.  Epidermis of human skin: pyroelectric and piezoelectric sensor layer. , 1982, Science.

[186]  Youngoh Lee,et al.  Skin-Inspired Hierarchical Polymer Architectures with Gradient Stiffness for Spacer-Free, Ultrathin, and Highly Sensitive Triboelectric Sensors. , 2018, ACS nano.

[187]  Jiasheng Dong,et al.  Using human hair follicle‐derived keratinocytes and melanocytes for constructing pigmented tissue‐engineered skin , 2011, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[188]  R J Minns,et al.  The role of the fibrous components and ground substance in the mechanical properties of biological tissues: a preliminary investigation. , 1973, Journal of biomechanics.

[189]  Nicholas A Kotov,et al.  Electrical stimulation of neural stem cells mediated by humanized carbon nanotube composite made with extracellular matrix protein. , 2009, Nano letters.

[190]  S. T. Lee,et al.  Fabrication and characterization of a sponge-like asymmetric chitosan membrane as a wound dressing. , 2001, Biomaterials.

[191]  S. Hollister.  Porous scaffold design for tissue engineering , 2005, Nature materials.

[192]  X. Gong,et al.  Novel Safeguarding Tactile e‐Skins for Monitoring Human Motion Based on SST/PDMS–AgNW–PET Hybrid Structures , 2018 .

[193]  Jian Ji,et al.  Construction of antibacterial multilayer films containing nanosilver via layer-by-layer assembly of heparin and chitosan-silver ions complex. , 2006, Journal of biomedical materials research. Part A.

[194]  Rongshun Chen,et al.  A flexible multifunctional tactile sensor using interlocked zinc oxide nanorod arrays for artificial electronic skin , 2018 .

[195]  Mitsuo Niinomi,et al.  Mechanical biocompatibilities of titanium alloys for biomedical applications. , 2008, Journal of the mechanical behavior of biomedical materials.

[196]  R. Langer,et al.  A tough biodegradable elastomer , 2002, Nature Biotechnology.

[197]  M. Kaltenbrunner,et al.  Ultraflexible organic photonic skin , 2016, Science Advances.

[198]  Phelps J. Lambert,et al.  Cutaneous signs of systemic disease. , 2011, Clinics in dermatology.

[199]  Konstantinos Sousounis,et al.  Organ repair and regeneration: an overview. , 2012, Birth defects research. Part C, Embryo today : reviews.

[200]  Krzysztof Matyjaszewski,et al.  Nanostructured functional materials prepared by atom transfer radical polymerization , 2009, Nature Chemistry.

[201]  Vikas Berry,et al.  Self-assembly of nanoparticles on live bacterium: an avenue to fabricate electronic devices. , 2005, Angewandte Chemie.

[202]  Shravanthi T. Reddy,et al.  Surface micropattern limits bacterial contamination , 2014, Antimicrobial Resistance and Infection Control.

[203]  Georges Griso,et al.  Mechanical modeling of the skin , 2011, Asymptot. Anal..

[204]  Karl R Edminster,et al.  Multi-layered culture of human skin fibroblasts and keratinocytes through three-dimensional freeform fabrication. , 2009, Biomaterials.

[205]  A. F. Recum,et al.  Applications and failure modes of percutaneous devices: A review , 1984 .

[206]  David T Corr,et al.  Biomechanics of Scar Tissue and Uninjured Skin. , 2013, Advances in wound care.

[207]  Timothy K Lu,et al.  Stretchable living materials and devices with hydrogel–elastomer hybrids hosting programmed cells , 2017, Proceedings of the National Academy of Sciences.

[208]  A. Patapoutian,et al.  Trp ion channels and temperature sensation. , 2006, Annual review of neuroscience.

[209]  E. Scilingo,et al.  Polymer based interfaces as bioinspired 'smart skins'. , 2005, Advances in colloid and interface science.

[210]  Yongfeng Lu,et al.  A wearable pressure sensor based on ultra-violet/ozone microstructured carbon nanotube/polydimethylsiloxane arrays for electronic skins , 2018, Nanotechnology.

[211]  Manuel A. Coimbra,et al.  Temperature dependence of the formation and melting of pectin–Ca2+ networks: a rheological study , 2003 .

[212]  Jinqing Wang,et al.  A Novel Wound Dressing Based on Ag/Graphene Polymer Hydrogel: Effectively Kill Bacteria and Accelerate Wound Healing , 2014 .

[213]  G. Whitesides,et al.  Components for integrated poly(dimethylsiloxane) microfluidic systems , 2002, Electrophoresis.

[214]  R. Reis,et al.  Poly(hydroxybutyrate-co-hydroxyvalerate) bilayer skin tissue engineering constructs with improved epidermal rearrangement. , 2014, Macromolecular bioscience.

[215]  C. Eisele,et al.  Water, Electrolyte and Nitrogen Content of Human Skin , 1945 .

[216]  Y. Lee,et al.  Skin thickness of Korean adults , 2002, Surgical and Radiologic Anatomy.

[217]  Fotios Papadimitrakopoulos,et al.  Biomaterials/Tissue Interactions: Possible Solutions to Overcome Foreign Body Response , 2010, The AAPS Journal.

[218]  Lingzhou Zhao,et al.  Antibacterial coatings on titanium implants. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[219]  Malcolm Xing,et al.  Skin‐Inspired Multifunctional Autonomic‐Intrinsic Conductive Self‐Healing Hydrogels with Pressure Sensitivity, Stretchability, and 3D Printability , 2017, Advanced materials.

[220]  A. Rawlings,et al.  Moisturization and skin barrier function , 2004, Dermatologic therapy.

[221]  S. Ramakrishna,et al.  Latent Oxidative Polymerization of Catecholamines as Potential Cross-linkers for Biocompatible and Multifunctional Biopolymer Scaffolds. , 2016, ACS applied materials & interfaces.

[222]  J. García-Verdugo,et al.  Production of human tissue‐engineered skin trilayer on a plasma‐based hypodermis , 2013, Journal of tissue engineering and regenerative medicine.

[223]  Silvestro Micera,et al.  Electronic dura mater for long-term multimodal neural interfaces , 2015, Science.

[224]  F. Auger,et al.  The pivotal role of vascularization in tissue engineering. , 2013, Annual review of biomedical engineering.

[225]  E. Hoek,et al.  A review of the antibacterial effects of silver nanomaterials and potential implications for human health and the environment , 2010 .

[226]  Nae-Eung Lee,et al.  Flexible Transparent Reduced Graphene Oxide Sensor Coupled with Organic Dye Molecules for Rapid Dual‐Mode Ammonia Gas Detection , 2016 .

[227]  F. D. Prez,et al.  Fifteen chemistries for autonomous external self-healing polymers and composites , 2015 .

[228]  Tal Dvir,et al.  Tissue–electronics interfaces: from implantable devices to engineered tissues , 2018 .

[229]  C. Seeliger,et al.  Low-frequency pulsed electromagnetic fields significantly improve time of closure and proliferation of human tendon fibroblasts , 2014, European Journal of Medical Research.

[230]  Xian Jun Loh,et al.  Injectable Supramolecular Hydrogels as Delivery Agents of Bcl‐2 Conversion Gene for the Effective Shrinkage of Therapeutic Resistance Tumors , 2017, Advanced healthcare materials.

[231]  B. Müller,et al.  Polydimethylsiloxane films engineered for smart nanostructures , 2018, Microelectronic Engineering.

[232]  J. Ying,et al.  Poly(3,4-ethylenedioxythiophene) (PEDOT) nanobiointerfaces: thin, ultrasmooth, and functionalized PEDOT films with in vitro and in vivo biocompatibility. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[233]  C. Anthony,et al.  Bio-hybrid tactile sensor for the study of the role of mechanoreceptors in human tactile perception , 2012 .

[234]  Benjamin C. K. Tee,et al.  25th Anniversary Article: The Evolution of Electronic Skin (E‐Skin): A Brief History, Design Considerations, and Recent Progress , 2013, Advanced materials.

[235]  Zibiao Li,et al.  Recent advances in stereocomplexation of enantiomeric PLA-based copolymers and applications , 2016 .

[236]  Gregory C. Rutledge,et al.  Spray‐Layer‐by‐Layer Carbon Nanotube/Electrospun Fiber Electrodes for Flexible Chemiresistive Sensor Applications , 2014 .

[237]  Vivek Subramanian,et al.  Inkjet‐Printed Flexible Gold Electrode Arrays for Bioelectronic Interfaces , 2016 .

[238]  M. Gupta,et al.  Depression and suicidal ideation in dermatology patients with acne, alopecia areata, atopic dermatitis and psoriasis , 1998, The British journal of dermatology.

[239]  Guorui Jin,et al.  Facile Layer-by-Layer Self-Assembly toward Enantiomeric Poly(lactide) Stereocomplex Coated Magnetite Nanocarrier for Highly Tunable Drug Deliveries. , 2016, ACS applied materials & interfaces.

[240]  M. Zilberman,et al.  Antibiotic-eluting medical devices for various applications. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[241]  Yei Hwan Jung,et al.  Injectable, Cellular-Scale Optoelectronics with Applications for Wireless Optogenetics , 2013, Science.

[242]  Allister F. McGuire,et al.  A skin-inspired organic digital mechanoreceptor , 2015, Science.

[243]  M. Pelliccia,et al.  Hyaluronan/Tannic Acid Nanoparticles Via Catechol/Boronate Complexation as a Smart Antibacterial System. , 2016, Macromolecular bioscience.

[244]  Xian Jun Loh,et al.  Polyhydroxyalkanoates: opening doors for a sustainable future , 2016 .

[245]  Chizhu Ding,et al.  A review of drug release mechanisms from nanocarrier systems. , 2017, Materials science & engineering. C, Materials for biological applications.

[246]  Erik H. Horak,et al.  Optical Microresonators for Sensing and Transduction: A Materials Perspective , 2017, Advanced materials.

[247]  Guoqiang Chen,et al.  Synthesis, Characterization and Cell Compatibility of Novel Poly(ester urethane)s Based on Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) and Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) Prepared by Melting Polymerization , 2009, Journal of biomaterials science. Polymer edition.

[248]  Y. Hao,et al.  Electronic Devices for Human‐Machine Interfaces , 2017 .

[249]  Zhenan Bao,et al.  Pursuing prosthetic electronic skin. , 2016, Nature materials.

[250]  Paul M. George,et al.  Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics. , 2005, Biomaterials.

[251]  W. Reichert,et al.  Polyimides as biomaterials: preliminary biocompatibility testing. , 1993, Biomaterials.

[252]  Sam Emaminejad,et al.  Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis , 2016, Nature.

[253]  F H Silver,et al.  Assembly of type I collagen: fusion of fibril subunits and the influence of fibril diameter on mechanical properties. , 2000, Matrix biology : journal of the International Society for Matrix Biology.

[254]  Jianshi Tang,et al.  Large-Area High-Performance Flexible Pressure Sensor with Carbon Nanotube Active Matrix for Electronic Skin. , 2018, Nano letters.

[255]  Hai-Long Jiang,et al.  A Stretchable Electronic Fabric Artificial Skin with Pressure‐, Lateral Strain‐, and Flexion‐Sensitive Properties , 2016, Advanced materials.

[256]  Yaping Zang,et al.  Advances of flexible pressure sensors toward artificial intelligence and health care applications , 2015 .

[257]  Bharat Bhushan,et al.  Biomimetics inspired surfaces for drag reduction and oleophobicity/philicity , 2011, Beilstein journal of nanotechnology.

[258]  Yei Hwan Jung,et al.  Stretchable silicon nanoribbon electronics for skin prosthesis , 2014, Nature Communications.

[259]  Zhenan Bao,et al.  Skin-inspired electronic devices , 2014 .

[260]  Ritu Raman,et al.  Three-dimensionally printed biological machines powered by skeletal muscle , 2014, Proceedings of the National Academy of Sciences.

[261]  Zhibin Yu,et al.  User-interactive electronic skin for instantaneous pressure visualization. , 2013, Nature materials.

[262]  Xuanhe Zhao,et al.  Stretchable Hydrogel Electronics and Devices , 2016, Advanced materials.

[263]  Paras R. Patel,et al.  Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces. , 2012, Nature materials.

[264]  K. Cheung.  Implantable microscale neural interfaces , 2007, Biomedical microdevices.

[265]  H. B. LlLLYWHITE,et al.  Surface sculpturing and water retention of elephant skin , 1987 .

[266]  Michael F Marmor,et al.  Localized neurotransmitter release for use in a prototype retinal interface. , 2003, Investigative ophthalmology & visual science.

[267]  L. Beccai,et al.  Development and characterization of a bio-hybrid skin-like stretchable electrode , 2011 .

[268]  B. Coulomb,et al.  Biotechnological Management of Skin Burn Injuries: Challenges and Perspectives in Wound Healing and Sensory Recovery. , 2016, Tissue engineering. Part B, Reviews.

[269]  T. Arie,et al.  Wearable, Human‐Interactive, Health‐Monitoring, Wireless Devices Fabricated by Macroscale Printing Techniques , 2014 .

[270]  Won-Hyeong Park,et al.  Crack-Enhanced Microfluidic Stretchable E-Skin Sensor. , 2017, ACS applied materials & interfaces.

[271]  Quankang Wang,et al.  A Bioinspired Mineral Hydrogel as a Self‐Healable, Mechanically Adaptable Ionic Skin for Highly Sensitive Pressure Sensing , 2017, Advanced materials.

[272]  C. McCaig,et al.  The direction of growth of differentiating neurones and myoblasts from frog embryos in an applied electric field. , 1981, The Journal of physiology.

[273]  R. Ghaffari,et al.  Recent Advances in Flexible and Stretchable Bio‐Electronic Devices Integrated with Nanomaterials , 2016, Advanced materials.

[274]  Alexandra G Martinez,et al.  Electrochemical sensing based on printable temporary transfer tattoos. , 2012, Chemical communications.

[275]  Ja Hoon Koo,et al.  Highly Skin‐Conformal Microhairy Sensor for Pulse Signal Amplification , 2014, Advanced materials.

[276]  Edoardo Mazza,et al.  Mechanical biocompatibility of highly deformable biomedical materials. , 2015, Journal of the mechanical behavior of biomedical materials.

[277]  C. Mu,et al.  Flexible Normal‐Tangential Force Sensor with Opposite Resistance Responding for Highly Sensitive Artificial Skin , 2018 .

[278]  M. C. Stuart,et al.  Emerging applications of stimuli-responsive polymer materials. , 2010, Nature materials.

[279]  Deepak Kumar,et al.  Flexible single walled nanotube based chemical sensor for 2,4-dinitrotoluene sensing , 2018, Journal of Materials Science: Materials in Electronics.

[280]  Buddy D Ratner,et al.  Biomaterials: where we have been and where we are going. , 2004, Annual review of biomedical engineering.

[281]  W. Dunne,et al.  Bacterial Adhesion: Seen Any Good Biofilms Lately? , 2002, Clinical Microbiology Reviews.

[282]  Young-Ah Woo,et al.  Determination of water content in skin by using a ft near infrared spectrometer , 2005, Archives of pharmacal research.

[283]  Cody J. Smith,et al.  Genetically targeted magnetic control of the nervous system , 2016, Nature Neuroscience.

[284]  Hyoyoung Lee,et al.  Flexible and Stretchable Optoelectronic Devices using Silver Nanowires and Graphene , 2016, Advanced materials.

[285]  P. Lucas,et al.  Ranking the fracture toughness of thin mammalian soft tissues using the scissors cutting test. , 1997, Journal of biomechanics.

[286]  Diego Velasco,et al.  3D bioprinting of functional human skin: production and in vivo analysis , 2016, Biofabrication.

[287]  G. Krijnen,et al.  Towards a high-resolution flow camera using artificial hair sensor arrays for flow pattern observations , 2012, Bioinspiration & biomimetics.

[288]  A. Chandrakasan,et al.  Energy extraction from the biologic battery in the inner ear , 2012, Nature Biotechnology.

[289]  Dae-Eun Kim,et al.  Non-volatile organic memory with sub-millimetre bending radius , 2014, Nature Communications.

[290]  James H. Smith,et al.  Micromachined pressure sensors: review and recent developments , 1997 .

[291]  Zibiao Li,et al.  Facile synthesis of RGD-conjugated unimolecular micelles based on a polyester dendrimer for targeting drug delivery. , 2017, Journal of materials chemistry. B.

[292]  Kenneth O. Johnson,et al.  Tactile Functions of Mechanoreceptive Afferents Innervating the Hand , 2000, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[293]  Jürgen Kosel,et al.  Magnetic Nanocomposite Cilia Tactile Sensor , 2015, Advanced materials.

[294]  K. Fan,et al.  A 32 × 32 temperature and tactile sensing array using PI-copper films , 2010 .

[295]  M. Kaltenbrunner,et al.  An ultra-lightweight design for imperceptible plastic electronics , 2013, Nature.

[296]  Benjamin C. K. Tee,et al.  Highly sensitive flexible pressure sensors with microstructured rubber dielectric layers. , 2010, Nature materials.

[297]  Pankaj Karande,et al.  Design and fabrication of human skin by three-dimensional bioprinting. , 2014, Tissue engineering. Part C, Methods.

[298]  F. Wood,et al.  The use of cultured epithelial autograft in the treatment of major burn injuries: a critical review of the literature. , 2006, Burns : journal of the International Society for Burn Injuries.

[299]  S. J. Kim,et al.  Biocompatibility of polyimide microelectrode array for retinal stimulation , 2004 .

[300]  Hidenobu Arimoto,et al.  Regional Difference of Water Content in Human Skin Studied by Diffuse-Reflectance Near-Infrared Spectroscopy: Consideration of Measurement Depth , 2006, Applied spectroscopy.

[301]  Steve Marschner,et al.  Microstructures to control elasticity in 3D printing , 2015, ACM Trans. Graph..

[302]  V. Wright,et al.  The directional effects of skin. A bio-engineering study of skin with particular reference to Langer's lines. , 1966, The Journal of investigative dermatology.