A Massachusetts General Hospital (MGH) research team has reported that repeated treatment with pulsed electric fields – a noninvasive procedure that does not generate heat – may help reduce the development of scarring. In the Journal of Investigative Dermatology, the investigators from the MGH Center for Engineering in Medicine (MGH-CEM) and collaborators describe how use of the technology – called partial irreversible electroporation – reduced scarring after burn injuries in an animal model and improved several skin properties by removal of excess skin cells.
“We showed that killing some, but not all of the cells in the wound could actually help regenerate skin without scarring,” says lead author Alexander Golberg, PhD, of the MGH-CEM. “The main difference between this approach and procedures like ultrasound and lasers is that they operate on the whole tissue, while pulsed electric field treatment works on only a cellular level, which we expect will provide more precise treatment results in the future as we are able to target cells specifically.” Golberg is also on the faculty of the Porter School of Environmental Studies at Tel Aviv University in Israel.
Current data suggest that scarring results from alterations in the responses of the many different tissues involved in wound healing, but despite significant recent progress in understanding the process, the exact molecular mechanisms of scar formation are not fully understood. As a result, the many therapeutic procedures developed to prevent or treat scarring – including surgical removal, steroid injections and laser therapy – have had limited success. MGH-CEM investigators have been studying the use of pulsed electric field (PEF) technology for the past five years and have demonstrated several novel applications – including disinfection of burn injuries and rejuvenation of skin – in animal models.
PEF induces the formation of tiny pores in cellular membranes, and while the process leads to the death of those cells, there is no damage to the extracellular matrix or to nearby blood vessels or other structures. In fact, PEF-induced cell death causes adjacent cells to proliferate and release factors promoting tissue growth and repair. For the current study, the MGH-CEM team determined the optimal strength, number of pulses and number of treatments required to reduce the formation of scars in rats that had experienced burn injuries under anesthesia. The results showed that five PEF treatment sessions spaced 20 days apart after burn injury reduced the size of scars by almost 58 percent and also improved several properties of the scars – including overall appearance and the structure, density and direction of collagen fibers.
“The progress of therapies to treat scars has been very slow, with very few new technologies in the area, mostly because of the complexity of the problem and the lack of suitable animal models,” says Martin Yarmush, MD, PhD, director of the MGH-CEM and senior author of the report. “We now need to investigate whether this new technology and approach will show results in human patients, and we are looking for funding to help us design, build and test a device for clinical application.”
Additional co-authors of the Journal of Investigative Dermatology paper are Martin Villiger, PhD, William Lo and Brett E. Bouma, PhD, Wellman Center for Photomedicine at MGH; Saiqa Khan, MD, and William G. Austen Jr, MD, MGH Plastic and Reconstructive Surgery; Kyle Quinn, PhD, Arkansas University; and Martin Mihm, MD, Brigham and Women’s Hospital. The study was supported by Shriners Hospitals for Children grant 85120-BOS.
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $800 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals, earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2016 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of “America’s Best Hospitals.”