Wounds That Never Heal: Can Internet of Things (IoT) Help?

Tumors are wounds that do not heal.                       -Harold Dvorak

Death due to cancers that stem from malignant tumors is an overwhelming number. A tumor is classified as a chronic wound. A recent study published in the Journal of American Medical Association (JAMA) claims that chronic wound affects 4.5 million people in the US. Detecting a chronic wound at the early stage is a challenge and quite often the late detection of these wounds lead to casualties. Over $20 billion is spent annually on the treatment of chronic wounds. With so much money at stake, coming up with low-cost or frugal biomedical innovations for detecting wound is a giant leap towards the cure.

What are Chronic Wounds?

Wounds that fail to proceed through the normal healing response or fail to produce the functional integrity within 3 months are called Chronic Wounds. Chronic wounds include ulcers like Diabetic Foot Ulcers and Venous Leg Ulcers.  Tumors and even deep burns are chronic wounds.

The chronic wounds usually have reduced angiogenesis, increased incidence of infection and prolonged inflammation. They also have delayed epithelialization and growth factors are expressed in insufficient numbers. The figure below above gives a contrast between a normal wound and a chronic wound.

Chronic Wound vs Normal Wound
The key differences between the normal wound healing environment and that of a chronic wound
Courtesy: Advances In Wound Care

IoT Based Wound Monitoring Devices in 2017-18

Chronic wounds are susceptible to infections and may lead to neurotraumatic limb amputation. 3 different research groups have come up with their independent and unique IoT based technologies to detect Chronic Wound in the last 1.5 years. Here is a brief insight into these three devices.

1. Smart Bandage For Monitoring of Wound

Smart Bandage For Chronic Wound Monitoring
Smart Bandage Developed By Researchers Led By Tufts University. This device has 2 components: electrical and a flexible patch.
Courtesy: Wiley Online Library

Wound surroundings are dynamic, especially the pH of the wound environment keeps on changing because pH regulates all the biochemical reactions taking place in the wound environment. In case of chronic wounds, it changes from acidic to alkaline over time. This is the fundamental principle behind the IoT-based device developed by a diverse group of researchers led by Tufts University.

The interdisciplinary research, published in the journal Small, aims at on-demand drug delivery to the wound site. The prototype consists of 2 parts: an electric unit and a flexible patch. The patch comprised pH sensors, flexible heaters and thermoresponsive polymeric material carrying the drug. The electronic component powers the sensors,  records the sensor data and contains a microcontroller to process the data measured by the sensors.




It is interesting to note that thermoresponsive polymers are known to switch their properties across the phase transition temperature in a suitable medium (usually organic solvents). for example, polystyrene behaves as a thermoresponsive polymer in cyclohexane.

In this prototype, the researchers used PNIPAM-based particles ( poly(N-isopropylacrylamide) ) embodied in alginate hydrogel as the thermoresponsive drug carrier. The hydrogel layer was cast on the top of the flexible heater so that the drug is released when the heater is turned on.

2. Inkjet Printed Smart Bandage With Wireless Monitoring

Low cost smart bandage for chronic wound
The smart bandage has two parts: lower disposable part and an upper reusable part. The wireless electronic circuit including the antenna has been inkjet printed. Courtesy: Nature Scientific Reports, Farooqui et al.

A team of researchers at the IMPACT Lab in KAUST, Saudi Arabia have developed a real-time wireless wound monitoring system that takes into consideration parameters like pH level, irregular bleeding and external pressure at the wound site to send early warnings for chronic wounds. A normal wound environment has pH around 5.5-6.5. However, for chronic wounds or wounds with bacterial infections, the pH is over 6.5.

According to an article published by the researchers from KAUST in the proceedings of 2016 IEEE MTT-S International Microwave Symposium, the bandage uses polyaniline based potentiometric sensor to detect wound. While the fundamental principle of wound detection using pH is the same as in the previous case, the fabrication technology of the sensor differentiates it from the other two smart bandages in this article.

3. Omniphobic Paper Based Smart Bandage

Steps to make the smart bandage
Steps to make the bandage. All the electronic components are embedded on the Whitman omniotic paper from GE Healthcare.  Courtesy: Pal et al.

Another team of researchers at Purdue University have recently come up with a single-use, omniphobic paper-based smart bandage that can monitor chronic wounds and detect the formation of pressure ulcers. Unlike the previous two devices which rely only on pH level of the wound environment, this device uses both the pH and uric acid levels to monitor the wound area.

Omniphobic paper is a surface-modified paper which can resist wetting by many organic liquids like blood. The surface of an omniphobic paper can be modified by treatment with a highly fluorinated alkylsilane. These special-grade papers have found use in microfluidic devices in the past one decade. The researchers from Purdue leveraged the special property of this paper and used it as the base on which the electronic components were embedded.

The researchers developed the low-cost electrochemical and impedance sensors (pH and uric acid sensors) using conductive inks from Applied Ink Solutions, giving an edge over their contemporaries. Traditionally, metal-oxide based pH sensors have been deployed for pH measurements. However, these traditional sensors fluctuate in sensitive areas and have a high cost of fabrication.

The sensors were powered by a rechargeable battery and controlled by Arduino Nano v3.0 microcontroller. The RF (Radio Frequency) transceiver (receiver+transmitter) performs wireless communication with a remote device like a smartphone. This is typical to any IoT based system.

The USP of the prototype is that it can be integrated with a commercially available BAND-AID. In fact, the researchers used a commercial grade BAND-AID from Johnson & Johnson Consumer Inc. Further, the smart bandage weighs roughly around 8 grams and costs around $18.

The researchers even successfully tested the smart bandage on a mouse model. According to the research published in the journal Biosensors and Bioelectronic , the researchers claim “We used ten laboratory mice with a mixed background to detect pressure induced tissue damage in vivo. Omniotic Paper Based Smart Bandages can be used to detect the formation of pressure ulcers even before they can be visually identified.”

Conclusion

These 3 IoT-based smart bandages can minimize the frequency of wound dressing, thus reducing the stress and pain suffered by the patient in this process. There are several other physio-chemical parameters like moisture, partial pressure of Oxygen and bacterial load that can be quantified to achieve a more accurate result with the biodemical diagnosis. One can also monitor wounds using non-invasive techniques like digital photography and ultrasound. However, these can’t be integrated into wearables.

The recent advances in flexible electronics can help in manufacturing a state-of-the-art smart bandage with multiple sensors integrated into the bandage.  Currently, these 3 smart bandages haven’t been put to use in clinical trials yet. In fact, currently, we don’t have a commercial grade FDA or CE approved smart bandage available in the market. Therefore, the results of the clinical trials of these 3 IoT-based devices would be interesting to watch out.

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