E-skin set to disrupt healthcare

  • The ‘needle’ has moved significantly since the FDA approved the first artificial human skin in 1996
  • Researchers in Australia have developed an electronic artificial skin (e-skin) that reacts to pain just like real skin 
  • Researchers in the US have developed an e-skin that mimics the functions and properties of human skin
  • These are just 2 examples of 100s of e-skin developments currently taking place around the world
  • Research findings on the functions and properties of e-skin pave the way for enhancing non-invasive alternatives to skin grafts, improving consumer healthcare, developing smarter prosthetics and advancing intelligent robotics
  • Such improvements are likely to take place over the next decade
  • One possible near-term application for e-skin is to enhance the Apple Watch
  • The commercial beneficiaries of e-skin are more likely to be giant tech companies rather than traditional manufacturers of medical devices
  
E-skin set to disrupt healthcare
 
 
In September 2020 researchers from Australia’s Royal Melbourne Institute of Technology (RMIT) published findings of a study entitled, “Artificial Somatosensors: Feedback Receptors for Electronic Skins” in Advanced Intelligent Systems. The study’s focus was an electronic artificial skin (e-skin) made of silicone rubber with integrated electronics with the capacity to mimic the functionality of real skin and almost instantaneously distinguish between less and more severe forms of pain. Just as nerve signals instantaneously travel to your brain to inform you that you have encountered something sharp or hot, the e-skin reported in this study triggers similar mechanisms to achieve comparable results. This represents a significant advance towards the next generation of biomedical technologies, non-invasive skin grafts, smart prosthetics and intelligent robotics: all large, underserved fast growing global markets.
 
A significant advance in bioengineering

According to Madhu Bhaskaran, the study’s lead author, a professor at RMIT and the co-leader of the University’s Functional Materials and Microsystems Research Group, the research is the first time that electronic technologies have been shown to mimic the human feeling of pain. “No electronic technologies have been able to realistically mimic that very human feeling of pain - until now. It’s a critical step forward in the future development of the sophisticated feedback systems that we need to deliver truly smart prosthetics and intelligent robotics,” said Bhakaran.
 
Her remarks were emphasised by Md Ataur Rahman, a researcher at RMIT who said, “We’ve essentially created the first electronic somatosensors - replicating the key features of the body’s complex system of neurons, neural pathways and receptors that drive our perception of sensory stimuli . . . . While some existing technologies have used electrical signals to mimic different levels of pain, our new devices can react to real mechanical pressure, temperature and pain and deliver the right electronic response . . . .  It means our artificial skin knows the difference between gently touching a pin with your finger or accidentally stabbing yourself with it - a critical distinction that has never been achieved before electronically.”
 
Combination of three smart technologies

The RMIT device combines three ”game-changing” technologies to deliver its superior sensing capabilities, all previously designed and patented by Bhakaran’s team. The first is a stretchable, transparent and unbreakable electronic device made of oxide materials and biocompatible silicone, which allows it to be as thin as a piece of paper. The second is a temperature-reactive coating that is, “1,000 times thinner than a human hair”, which can transform when it comes into contact with heat. The third is a “brain-mimicking memory”, which facilitates electronic cells to simulate your brain’s ability to remember temperature and pain thresholds and store these in its own long-term memory bank. Further development is required to integrate these technologies into biomedical applications and demonstrate their stability over time, but crucially says Bhaskaran, “the fundamentals - biocompatibility, skin-like stretchability - are already there."
 
E-skin research has been progressing for decades

E-skin research is not new and has been developing for at least the past three decades. Here we cannot do justice to the breadth and depth of such research, but we can give a flavour of its history and briefly describe another e-skin that mimics human skin, which was reported in the February 2018 edition of Science Advances.
 
As early as the 1970s, researchers were exploring the potential application of tactile‐sensing simulation and had demonstrated certain touch sensors, but with low resolution and rigid materials. Notwithstanding, over the ensuing two decades significant breakthroughs were achieved in malleable and stretchable electronic devices for various applications. More recently, tactile sensors with enhanced performance have been developed based on different physical transduction mechanisms, including those affecting: (i) the change in the electrical resistivity of a semiconductor or metal when mechanical strain is applied (piezoresistivity), (ii) the ratio of the change in electric charge of a system to the corresponding change in its electric potential (capacitance), and (iii) the electric charge that accumulates in certain solid materials in response to applied mechanical stress (piezoelectricity). Parallel to these advances, significant progress also has been made in design, manufacturing, electronics, materials, computing, communication and systems integration. Together, these developments and technologies open new areas for applications of bioengineered systems.
 
Breakthrough e-skin by a US group

The 2018 e-skin research study reported in Science Advances was led by Jianliang Xiao, a Professor of Mechanics of Materials and Wei Zhang, a Professor of Chemistry, both from the University of Colorado Boulder. They describe the characteristics of their e-skin, as “thin, translucent, malleable and self-healing and mimics the functions and properties of human skin.” Reportedly the e-skin has several distinctive properties, including a novel type of molecular bond, known as polyamine, that involves the sharing of electron pairs between atoms, which the researchers have embedded with silver nanoparticles to provide enhanced mechanical strength, chemical stability and electrical conductivity. “What is unique here is that the chemical bonding of polyamine we use allows the e-skin to be both self-healing and fully recyclable at room temperature,” said Xiao. Further, the e-skin’s malleability enables it to permanently conform to complex, curved surfaces without introducing excessive interfacial stresses, which could be significant for its development. The Boulder group has created a number of different types and sizes of their wearable e-skin, which are now being tested in laboratories around the world.
 
In the Commentary

In this Commentary we not only report the research findings of the two e-skin studies mentioned above, but we also describe, in simple terms, how you experience pain to illustrate the achievement of the Australian researchers from RMIT. We then describe human skin, its capacity to be wounded and traditional skin graft therapies to deal with such wounds. We briefly reference the invention of the first artificial human skin to receive FDA approval and highlight some of the massive and significant technological and market changes that have taken place since then. We conclude by suggesting that, over the next decade as e-skin technologies are enhanced, their potential healthcare applications are more likely to be owned and controlled by giant tech companies than traditional manufacturers of medical devices. More about this later. In the meantime, let us return to Bhakaran’s new pain-sensing e-skin and briefly describe the devilishly complex functionality of how you experience pain.
The function of pain and how you experience it
 
Your skin constantly senses things and your sensitivity to pain helps in both your survival and your protection. Pain prompts reflex reactions that prevent damage to tissue, such as quickly pulling your hand away from something when you feel pain. Notwithstanding, your pain response only begins when a certain threshold is breached. For example, you do not notice pain when you pick up something at a comfortable temperature, but you do when you prick your finger or touch something too hot. Consider this brief, over-simplified, description of how you experience pain.


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When you prick your finger on something sharp it causes tissue damage, which is registered by microscopic pain receptors in your skin. These send electrical signals through your nerve fibres that are bundled together with others to form a peripheral nerve. These electrical signals pass up your peripheral nerve and spinal cord to your neck area. Here they are transferred from one nerve cell to another by means of chemical messengers. The signals are then passed to three areas of your brain: one, the somatosensory cortex, that deals with physical sensation, another, the frontal cortex, which is linked with your thinking and a third area, your limbic system, which is associated with your emotions. All this occurs in nano seconds and results in you instantaneously feeling pain, wincing and becoming irritated when a pin pricks your finger.
 
Human skin and traditional skin grafts

Skin is your body’s largest and most versatile organ, which is unlike any other, not least because you wear it on the outside of your body. Not only is your skin a huge sensor packed with nerves for keeping your brain in touch with the outside world, it provides you with free movement. Adults carry  between 1.5 and 2.0 square metres of skin on their bodies, which weighs about 3.5kgs (≈16% of your body weight). Your skin is a “smart”, multifunctional organ that not only serves as a protective shield against heat, light, injury and infection, but also it is a sensory organ that regulates body temperature, stores water and fat, prevents water loss and helps to produce vitamin D when exposed to the sun. Skin wounds are relatively common and can be caused by trauma, skin diseases, burns or removal of skin during surgery. In the US alone, each year some 35m cases require clinical intervention for major skin loss.Your skin has three layers. The thin, outer layer that is visible to the eye is called the epidermis and the deeper two layers are called the dermis and hypodermis. Due to the presence of stem cells, a wound to your epidermis is able to stimulate self-regeneration. However, in cases of deeper injuries and burns, the process of healing is less efficacious and leads to chronic wounds. Any loss of full-thickness skin more than 4cm diameter needs to be treated immediately. Traditional ways of dealing with significant losses of skin have been skin grafts. The most common is to use either your own shin (autograft) or the skin from another person (allograft). Skin  grafts can also be obtained from a non-human source, usually a pig (xenograft). Autographs suffer from the fact that you may not have enough undamaged skin to treat the severity of your injury. Allografts and xenografts suffer from the possibility of rejection or infection. These challenges drove a need to develop an artificial skin.
 
The first FDA approved artificial human skin

The first artificial human skin to receive FDA approval was invented in the late-1970s by John Burke, a Professor of Surgery at the Harvard University Medical School and Chief of Trauma Services at Massachusetts General Hospital and Ioannis Yannas, a Professor of Polymer Science and Engineering at the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts. Burke had treated many burn victims and realized the need for a human skin replacement. Yannas had been studying collagen, a protein found in human skin. In the mid-1970s the two professors teamed-up to develop a material - an amalgam of plastics, cow tissue and shark cartilage - that became the first commercially reproducible, artificial human skin with properties to resist infection and rejection, protect against dehydration and significantly reduce scarring. In 1979 Burke and Yannas used their artificial skin on a woman patient, whose burns covered over half her body. In the early 1990s the Burke-Yannas skin was acquired by Integra LifeSciences Corporation. In March 1996 the company received FDA approval for it to be used on seriously burned patients, and Integra Artificial Skin became the first tissue regeneration product to reach the market. Since then, it has been used in therapies throughout the world and has saved and enhanced the lives of innumerable severely burned people. More recently, the Integra Artificial Skin has also been used in a number of other indications.
 
Technological advances and market changes since the first artificial skin

Since Integra’s launch of the first FDA approved artificial human skin, healthcare markets and technolgies have changed radically. In the mid-1970s when Professors Burke and Yannas came together to develop their artificial skin, Apple and Microsoft, two giant tech companies with interests in healthcare, were relatively small start-ups, respectively founded in 1976 and 1975.  it would be more than another  decade before Tim Berners-Lee invented the World Wide Web (1989), and then another decade before the internet became mainstream. The tech giants, Amazon and Google, also with interests in healthcare, were not founded until some years after that: 1994 and 1998 respectively. Over the past four decades substantial progress has been made in tissue engineered skin substitutes made from both artificial and natural materials by employing advances in various fields such as polymer engineering, bioengineering, stem cell research, nanomedicine and 3D bioprinting. Notwithstanding, a full thickness bioengineered skin substitute with hair follicles and sweat glands, which can vascularize rapidly is still not available. 
 
Market changes, e-skin, the Apple Watch and giant tech companies

In closing, we briefly focus on one potential near-term application for e-skin - to enhance the capabilities of the Apple Watch.  We do this to emphasise the significant market shifts, which are occurring in healthcare and the large and growing impact that giant tech companies are having on the sector.

The Apple Watch was first released in April 2015 by Tim Cook, Apple’s CEO, as a fashion accessory. Notwithstanding, its focus quickly shifted and within three years it had become a FDA approved medical device. The watch, not only can detect falls, but it also has 3 heart monitoring capabilities: one recognises and sounds an alarm when your heart rate is low, a second detects irregular heart rhythms and a third is a personal electrocardiogram (ECG), which is a medical test that detects heart problems by measuring the electrical activity generated by your heart as it contracts. According to Strategy Analytics, a consumer research firm, in 2019, an estimated 30.7m Apple Watches were sold worldwide; 36% higher than the 22.5m watches Apple sold in 2018.

In 2020, during the coronavirus public health emergency, the FDA expanded its guidance for non-invasive patient-monitoring technologies, including the Apple Watch’s ECG function. This expanded use is intended to help facilitate patient monitoring while reducing patient and healthcare provider contact and exposure to CoVID-19.
 
Currently, the Apple Watch is worn like any other watch and if it is loose, its data harvesting capacity could be compromised. In the form of a watch, e-skin would conformally adhere to irregularly shaped surfaces like your wrist. The two e-skins described in this Commentary; both with intrinsic stretchability could potentially facilitate the Apple Watch to be more integrated with the wearers own skin.

The unstoppable march of giant tech companies into healthcare
 
Today, not only do giant tech companies such as Apple, Amazon, Google and Microsoft have their global market presence as a significant comparative advantage to enter and expand into healthcare, but they also have unparalleled data management capabilities. Since the invention of artificial skin by Burke and Yannas healthcare has become digital and global. Because giant tech companies’ have superior access to individuals’ data and state-of-the-art data handling capabilities; they know customers/patients significantly better than any healthcare provider. This, together with their global reach, positions giant tech companies to provide discerning patients with the healthcare solutions they need and increasingly demand.
 
IBM Watson Health estimates that by the end of 2020, the amount of medical data we generate will double every 73 days. According to Statistica, an analytical software platform, new healthcare data generated in 2020 are projected to be 2,314 exabytes. Traditional healthcare providers cannot keep up with this vast and rapidly growing amount of health information, despite the fact that such information is increasingly significant as healthcare shifts away from its traditional focus on activity and becomes more outcomes/solutions orientated. Giant tech companies are on the cusp of meeting a large and growing need to understand, structure and manage health data to build a new infrastructure for the future of healthcare.
 
Takeaways

The potential impact of e-skin is significantly broader than enhancing the Apple Watch. The research findings reported in this Commentary suggest that e-skin is well positioned to disrupt substantial segments of healthcare over the next decade. Findings published in Advanced Intelligent Systems and Science Advances suggest that one potential application is for e-skin to be seamlessly integrated with human skin. This not only positions it to become the next generation for a number of traditional MedTech applications, such as non-invasive skin grafts, but also to deliver a step change in the consumer health market by producing breakthroughs in human-machine interfaces, health monitoring, transdermal drug delivery, soft robotics, prosthetics and health monitoring. If traditional manufacturers are to benefit from e-skin they will need to adapt and transform their processes because the natural fit for e-skin technologies is industry 4.0, [also referred to as smart manufacturing and the Internet of Things (IoT)], which is expected to become more pervasive over the next decade as developments of e-skin unfold. Industry 4.0 combines physical production and operations with smart digital technology, machine learning and big data to create more solution orientated healthcare ecosystems and thereby tends to favour the giant tech companies and their growing healthcare interests.
 
#e-skin #artificialskin #AppleWatch 

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