New device reduces scarring in damaged blood vessels

 

November 20, 2014

Northwestern University

A new device contains a form of vitamin A that controls inflammatory responses, preventing scar tissue formation and promoting wound healing. The soft, porous, and thin elastic material contains an acid form of vitamin A, called a retinoid, which is produced by the body to help cells develop and stay healthy. Synthetic retinoids have been formulated and traditionally used to treat acne and some types of cancer.

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When blood vessels are damaged through surgery, it can trigger an endless cycle of scarring and repair.

"Scar tissue will always form inside the blood vessel and, in many cases, eventually block blood flow," said Guillermo Ameer, professor of biomedical engineering at Northwestern University's McCormick School of Engineering. "Then surgeons have to go back in, eliminate the obstruction, or put in a new graft or stent to restore blood flow. In the case of a prosthetic vascular graft used for bypass surgery, it will scar again and ultimately fail."

Ameer, who is also professor of surgery at the Feinberg School of Medicine, has developed a new material that, when applied to damaged blood vessels, can prevent scarring and stop the cycle before it begins.

The soft, porous, and thin elastic material contains an acid form of vitamin A, called a retinoid, which is produced by the body to help cells develop and stay healthy. Synthetic retinoids have been formulated and traditionally used to treat acne and some types of cancer. Unfortunately, the oral dose needed to positively affect vessel healing and prevent scarring could never be administered to humans as it is toxic in very high doses.

"We solved this problem by using engineering and biomaterial science concepts," Ameer said. "We incorporated the retinoid into a biodegradable membrane that can be handled and implanted by a surgeon. That way, we can target the blood vessel and safely get the effect we want."

The research is described in the paper "Periadventitial atRA citrate-based polyester membranes reduce neointimal hyperplasia and restenosis after carotid injury in rats," which was published in the September 19 issue of the American Journal of Physiology: Heart and Circulatory Physiology. Elaine Gregory, research associate in surgery, and Antonio Webb, a former postdoctoral researcher in Ameer's lab and current professor at the University of Florida, were the paper's first authors.

Ameer started with an inherently antioxidant, citrate-based polymer previously developed in his laboratory. Then he added the all-trans retinoic acid (atRA), a vitamin A derivative. Ameer's longtime collaborator and co-senior author of the paper, Melina Kibbe, the Edward G. Elcock Professor of Surgical Research at Feinberg, evaluated the membrane in an animal model. When wrapped around the outside of a damaged blood vessel, it created a favorable environment for the healing process. Ameer and Kibbe noted a 50-60 percent reduction of scar formation compared to vessels without the membrane.

"We're putting something on the outside of the vessel that affects what happens inside the vessel," Ameer said. "It seems counterintuitive, but scarring also involves cells that are normally present on the outside layer of the blood vessel."

Damaged cells typically produce aggressive signals that cause their neighboring cells to become inflamed. Ameer said the material "keeps the cells quiet," so dangerous messages do not spread to the rest of the vessel. The membrane achieves local exposure to atRA, protecting the blood vessel and regulating how it responds to injury.

"Whether or not you employ a stent or attach a prosthetic graft to a blood vessel, you injure it," Ameer said. "The vessel's response to the injury can get out of control. With this fairly simple method, we are trying to control the inflammatory response and maintain adequate blood flow through the vessel."

 

 

Story Source:

The above story is based on materials provided by Northwestern University. The original article was written by Amanda Morris. Note: Materials may be edited for content and length.

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Journal Reference:

1. E. K. Gregory, A. R. Webb, J. M. Vercammen, M. E. Flynn, G. A. Ameer, M. R. Kibbe. Periadventitial atRA citrate-based polyester membranes reduce neointimal hyperplasia and restenosis after carotid injury in rats. AJP: Heart and Circulatory Physiology, 2014; 307 (10): H1419 DOI: 10.1152/ajpheart.00914.2013

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Northwestern University. "New device reduces scarring in damaged blood vessels." ScienceDaily. ScienceDaily, 20 November 2014. <www.sciencedaily.com/releases/2014/11/141120141804.htm>.

Paint on 'smart' bandage emits phosphorescent glow for healing below

 

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The transparent liquid bandage displays a quantitative, oxygenation-sensitive colormap that can be easily acquired using a simple camera or smartphone.

Inspired by a desire to help wounded soldiers, an international, multidisciplinary team of researchers led by Assistant Professor Conor L. Evans at the Wellman Center for Photomedicine of Massachusetts General Hospital (MGH) and Harvard Medical School (HMS) has created a paint-on, see-through, "smart" bandage that glows to indicate a wound's tissue oxygenation concentration. Because oxygen plays a critical role in healing, mapping these levels in severe wounds and burns can help to significantly improve the success of surgeries to restore limbs and physical functions. The work was published today in The Optical Society's (OSA) open-access journal Biomedical Optics Express.

"Information about tissue oxygenation is clinically relevant but is often inaccessible due to a lack of accurate or noninvasive measurements," explained lead author Zongxi Li, an HMS research fellow on Evans' team.

Now, the "smart" bandage developed by the team provides direct, noninvasive measurement of tissue oxygenation by combining three simple, compact and inexpensive components: a bright sensor molecule with a long phosphorescence lifetime and appropriate dynamic range; a bandage material compatible with the sensor molecule that conforms to the skin's surface to form an airtight seal; and an imaging device capable of capturing the oxygen-dependent signals from the bandage with high signal-to-noise ratio.

This work is part of the team's long-term program "to develop a Sensing, Monitoring And Release of Therapeutics (SMART) bandage for improved care of patients with acute or chronic wounds," says Evans, senior author on the Biomedical Optics Express paper.

How exactly does a 'smart' bandage work?

For starters, the bandage's not-so-secret key ingredient is phosphors -- molecules that absorb light and then emit it via a process known as phosphorescence.

Phosphorescence is encountered by many on a daily basis -- ranging from glow-in-the-dark dials on watches to t-shirt lettering. "How brightly our phosphorescent molecules emit light depends on how much oxygen is present," said Li. "As the concentration of oxygen is reduced, the phosphors glow both longer and more brightly." To make the bandage simple to interpret, the team also incorporated a green oxygen-insensitive reference dye, so that changes in tissue oxygenation are displayed as a green-to-red colormap.

The bandage is applied by "painting" it onto the skin's surface as a viscous liquid, which dries to a solid thin film within a minute. Once the first layer has dried, a transparent barrier layer is then applied atop it to protect the film and slow the rate of oxygen exchange between the bandage and room air -- making the bandage sensitive to the oxygen within tissue.

The final piece involves a camera-based readout device, which performs two functions: it provides a burst of excitation light that triggers the emission of the phosphors inside the bandage, and then it records the phosphors' emission. "Depending on the camera's configuration, we can measure either the brightness or color of the emitted light across the bandage or the change in brightness over time," Li said. "Both of these signals can be used to create an oxygenation map." The emitted light from the bandage is bright enough that it can be acquired using a regular camera or smartphone -- opening the possibility to a portable, field-ready device.

Immediate applications and future goals

Immediate applications for the oxygen-sensing bandage include monitoring patients with a risk of developing ischemic (restricted blood supply) conditions, postoperative monitoring of skin grafts or flaps, and burn-depth determination as a guide for surgical debridement -- the removal of dead or damaged tissue from the body.

"The need for a reliable, accurate and easy-to-use method of rapid assessment of blood flow to the skin for patients remains a clinical necessity," said co-author Samuel Lin, an HMS associate professor of surgery at Beth Israel Deaconess Medical Center. "Plastic surgeons continuously monitor the state of blood flow to the skin, so the liquid-bandage oxygenation sensor is an exciting step toward improving patient care within the realm of vascular blood flow examination of the skin."

What's the next step for the bandage? "We're developing brighter sensor molecules to improve the bandage's oxygen sensing efficiency," said Emmanuel Roussakis, another research fellow in Evans' laboratory and co-author, who is leading the sensor development effort. The team's laboratory research will also focus on expanding the sensing capability of the bandage to other treatment-related parameters -- such as pH, bacterial load, oxidative states and specific disease markers -- and incorporating an on-demand drug release capacity.

"In the future, our goal for the bandage is to incorporate therapeutic release capabilities that allow for on-demand drug administration at a desired location," says Evans. "It allows for the visual assessment of the wound bed, so treatment-related wound parameters are readily accessible without the need for bandage removal -- preventing unnecessary wound disruption and reducing the chance for bacterial infection."

Beyond the lab, the team's aim is to move this technology from the bench to the bedside, so they are actively searching for industry partners. They acknowledge research support from the Military Medical Photonics Program from the U.S. Department of Defense, and National Institutes of Health.

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Story Source:

The above story is based on materials provided by The Optical Society. Note: Materials may be edited for content and length.

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Journal Reference:

1. Zongxi Li, Emmanuel Roussakis, Pieter G. L. Koolen, Ahmed M. S. Ibrahim, Kuylhee Kim, Lloyd F. Rose, Jesse Wu, Alexander J. Nichols, Yunjung Baek, Reginald Birngruber, Gabriela Apiou-Sbirlea, Robina Matyal, Thomas Huang, Rodney Chan, Samuel J. Lin, and Conor L. Evans. Non-invasive transdermal two-dimensional mapping of cutaneous oxygenation with a rapid-drying liquid bandage. Biomed. Opt. Express, 5, 3748-3764 (2014) [link]

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