Opening a New Window to Wound Healing

  WATCH: Author Zongxi Li, PhD discusses the article.

  With the development of new tools and technology, wound dressings in the near future may no longer rely on wrapping wounds and passively waiting days for treatment assessment. Wound care researchers and clinicians at the Wellman Center for Photomedicine at Massachusetts General Hospital in Boston are developing a SMART (Sensing, Monitoring and Release of Therapeutics) interactive, noninvasive wound dressing that will function as a wearable biosensor that can “tell” caregivers the healing status of wounds. In response to visible changes or alerts from the bandage, caregivers will be able to trigger the dressing’s on-demand release of therapeutics for customized interventions. This article will discuss the mechanisms of action for the SMART bandage; its clinical adoption potential; and the anticipated impact this type of technology could have on patients, providers, and the industry as a whole.

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Wound Monitoring: An Unmet Clinical Need

  In the US alone, 6 million people develop chronic wounds each year, adding a treatment cost of more than $25 billion.¹ One of the main causes is diabetes: Patients with impaired peripheral circulation tend to develop chronic ulcers in the feet, ankles, and legs due to lower limb ischemia. It is estimated that a lower limb is lost somewhere in the world as a consequence of diabetes every 30 seconds.² Problematically, hypoxic wounds such as diabetic ulcers have long recovery times and sometimes will not heal at all.³ If identified early, hypoxic wounds can be addressed with treatments that target wound oxygenation and supplement growth factors to give patients more rapid healing rates. However, it is currently difficult to identify hypoxic wounds, as there is a lack of technology that can closely and objectively monitor wound oxygen concentration, also known as oxygen tension or pO₂.

  The current method for obtaining a patient’s oxygenation status in the clinic is pulse oximetry, an optical technique based on the absorption spectrum of hemoglobin. By shining two wavelengths of light, typically 660 nm and 940 nm, through a thin body part, the oxygen saturation value (not pO₂) can be extracted from the measured ratio between oxy- and deoxyhemoglobin in the arterial blood. Pulse oximetry probes are usually clamped onto the fingertip and monitor the overall systemic oxygen saturation of the patient. However, this approach does not provide the oxygenation of specific regions on the body, such as the tissue near an ulcerous wound.

  An alternative oxygen-sensing technology is the TcPO2 device, which measures transcutaneous pO₂ via an electrochemical probe fixed at a single point on the skin surface. This technology requires calibration for use in the wound care workflow, and therefore has not become a standard of care.

  Current clinical assessment of wounds requires dressing removal, which is often painful, disruptive to the wound bed, and can be detrimental to the healing process. A bandage capable of displaying wound-status information (eg, pO₂) across entire wound beds to patients and caregivers could revolutionize the management of chronic wounds, especially in early identification and intervention of problematic wounds.

  The bandage is disposable, transparent, and sterile. Additionally, it is painless to apply and remove. This intuitive technology is smartphone-compatible and will offer features that provide wound management professionals with continuous information on wound healing progress and various associated parameters such as tissue oxygenation, states of inflammation, and/or bacterial infection. For example, a SMART bandage system can display quantitative maps of pO₂ across an entire wound bed.

  In order to monitor tissue oxygen tension through intact skin, a prototype transdermal oxygen-sensing bandage has been developed and successfully tested in animal models, demonstrating its ability to identify tissue hypoxia.⁴ In the near future, the bandage will be engineered to sense other parameters and incorporate therapeutic release capability. If the bandage senses problems with the wound, caregivers will be able to trigger an on-demand release of anti-inflammatories, antibiotics, or healing-promoting biotics such as growth factors and platelet-rich fibrin.

Explaining Functionality

  By incorporating small molecule optical sensors into transparent bandage materials, the SMART bandage is, first of all, a wearable sensor that changes color to report healing-related tissue parameters. For example, the first prototype oxygen-sensing bandage is designed to glow upon blue-light illumination.

  When the bandage senses “normal” tissue oxygen tension (eg, transcutaneous pO₂ > 50 mmHg), it glows green. As the amount of oxygen in the tissue drops, the color gradually shifts to bright red. This signal can be visualized by the naked eye or with a compact detection device such as a smartphone or other mobile healthcare tools. The relative red-to-green intensity ratio can be calibrated to provide a quantitative measurement of oxygen concentration. This approach can be extended to other optical molecular sensors that, when integrated into the bandage, can provide additional wound information such as pH, bacterial load, and inflammation.

  Aside from providing an informative “window to the wound,” treatment can be provided in response to the detection of a compromised wound condition without dressing removal. By incorporating therapeutic agents into the bandage, Wellman researchers are engineering on-demand drug-release methods that can be triggered at specific wound locations (eg, regions reported by the bandage to be inflamed or infected).

  A significant advantage of this technology will be that sensing components are simple and inexpensive. Adding these features to an existing wound dressing has the potential to create low-cost monitoring solutions. Additionally, patients, perhaps with the assistance of a caregiver, could use a smartphone app to capture images of the bandage to get real-time assessment of their wounds.

Clinical Impact on Outpatient Care

  The oxygen-sensing SMART bandage is specifically designed to avoid the need to purchase and operate equipment that could be considered bulky and/or expensive in order to meet the unique challenges of measuring oxygen in outpatient, ambulatory, and home settings. By displaying pO₂ through a simple green-red colorimetric change, the bandage is intended to require minimal staff training, which could open its usage beyond physicians and nurses to patients themselves. Outpatient clinical uses of the bandage are anticipated to range from the surgical suite, where it can be expected to augment or replace perfusion measurement methods, to postoperative management and monitoring. As the bandage displays wound status via an easy-to-read color change that can be seen by the eye, it may also aid in the monitoring of multiple patients during recovery. Given its ease of application, the bandage will conceivably benefit patients as a point-of-care diagnostic administered during routine outpatient visits. A bandage preloaded with antibiotics or anti-inflammatories also would be useful in outpatient settings, as information relayed by the bandage could be put to immediate use without the need for bandage removal or systemic drug administration.

  Outside the clinic, the bandage is envisioned to be a standalone tool that can be used along with smartphones and/or tablets for home care. This is thought to be especially beneficial for the diabetic population, as the oxygenation and perfusion of lower limbs, for example, can be monitored as part of routine surveillance. The use of a smartphone app could provide real-time instruction to patients and caregivers, and relay images acquired from the bandage to physicians.

  In this way, using the oxygen-sensing bandage as a home diagnostic may reduce the number of unnecessary hospital visits, which may be of particular interest to those clinics affiliated with an accountable care organization. At the same time, home assessment may aid in the early diagnosis of ischemic abnormalities in those living with diabetes, enabling timely interventions that may prevent the need for hospitalization and advanced care.

Discussing the Clinician’s Role

  Initially envisioned to complement existing clinical workflows, the bandage, depending on need, may also serve to augment or replace current indirect measurements of perfusion such as laser Doppler and fluorescence angiography – tools that indicate blood flow but do not provide metrics of tissue pO₂. Similarly, the bandage may also serve to complement or replace near-infrared imaging, which reports blood oxygen saturation and not tissue oxygen tension.

  Unlike these complex tools that can require a dark operating room, trained technicians, or intravenous agent injection, the SMART bandage is simple to apply and can be used in bright, even sunlit rooms, offering ease of use and significant benefits in patient care. At this stage of development, wound care providers can play an immense role in shaping the future of the bandage technology by participating, designing, and performing tests and trials; aiding in comparison of the bandage with existing technology; and helping to identify gaps and needs that require greater innovation.

Pathway to Production

  The culmination of these efforts in the development of the first-generation oxygen-sensing bandage prototype has recently been published.⁴ The SMART bandage is currently positioned in the “feasibility/development” stage on the translational research path. Over the past two years, researchers have worked closely with the Translational research Core at the Wellman Center and the office of Partners HealthCare Innovation. The Translational Research Core works closely with individual labs at the Wellman Center, facilitating and accelerating transition of technological and medical research to clinical practice. Partners HealthCare Innovation is an organization that seeks to bring together specialists in medical technology licensing, research contracts, ventures, and business development to partner with investigators, scientists, and clinicians to introduce new technology into healthcare practice via a variety of business channels.

  The development of the SMART bandage platform represents what the authors consider to be a major multidisciplinary effort involving the research team as well as clinical partners, regulatory officials, and business-development and intellectual property experts. As of press time for Today’s Wound Clinic, the key technologies found within this product are being covered by a growing portfolio of patents filed in 2013 and 2014. Preclinical testing has indicated the bandage is safe when used in animals. Therefore, regulatory approval in the US for this device may be relatively straightforward and is anticipated within the next 3-5 years.

  Currently, researchers at the Wellman Center are in the process of initiating first in-human trials and negotiating licensing options with startups and small and large medical device companies. The key will be to identify commercial partners interested in bringing the technology to the market. The goal will be to establish a pathway that continues to sustain further innovation in the SMART bandage technology while supporting a collaborative scheme for technology development and handoff for eventual large-scale deployment.

Zongxi Li joined the Wellman Center for Photomedicine in 2012. Her current research focuses on the development of biocompatible sensors and imaging systems for monitoring oxygen and other physiological parameters in humans.

Gabriela Apiou-Sbirlea is assistant professor of dermatology at Harvard Medical School and director of the Translational Research Core for Wellman Center for Photomedicine. Her professional experience is centered on the application of physics and engineering principles to resolve clinical problems that involve biotechnology and medical gases with a specific focus on inhaled therapeutics and delivery devices.

Conor L. Evans is an assistant professor at the Wellman Center for Photomedicine. His research is focused on the development and clinical translation of optical microscopy and spectroscopy tools, with specific interests in ultrasensitive detection of molecular markers, label-free imaging of tissues, and the imaging and quantification of tissue oxygenation. He may be reached evans.conor@mgh.harvard.edu.

References

1. Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT. Human skin wounds: A major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17(6):763–771.

2. Boulton AJM, Vileikyte L, Ragnarson, Tennvall G, Aplelqvist J. The global burden of diabetic foot disease. Lancet. 2005; 366(9498):1721-1726.

3. Bishop A. Role of oxygen in wound healing. J Wound Care. 2008;17(9):399–402.

4. Li Z, Roussakis E, Koolen PGL, Ibrahim AMS, Kim K, Rose LF, et al. Non-invasive transdermal two-dimensional mapping of cutaneous oxygenation with a rapid-drying liquid bandage. Biomed Opt Express. 2014;5(11):3748-3764.