First in a series of four profiles on the 2017 winners of the BWH Health & Technology Innovation Grants. Each winning team competed in a “Shark Tank”-style event, and was selected for a $50,000 grant for basic/clinical/translational science-focused as well as commercialization-oriented research projects. These grants are supported by the Brigham Research Institute and the BWH Health & Technology Sub-Committee, which comprises friends of the Brigham from the philanthropic world.
Patients suffering from severe burn injuries have among some of the highest mortality rates in medicine. When treating severe burns, skin transplants are needed for wound closure and healing; however, the options for skin substitutes are extremely limited. Cadaveric skin (skin from a deceased person) is the closest biological skin substitute that a care team can use to treat a patient with severe burn injuries. However, the skin transplant recipient’s body will reject the cadaveric skin in a short window of time, usually within 10 days, making this procedure only a stopgap solution for patients. For other kinds of transplants, immunosuppressive drugs are typically administered to prevent rejection, but because of high risk of infection, severe burn patients cannot tolerate the drugs to accept the skin replacement.
Reza Abdi, MD, a transplant nephrologist of the Division of Renal (Kidney) Medicine, recognized the need to improve the outcome of skin transplants. Abdi, who is also a researcher interested in transplant rejection and immune suppression, is working to find new ways to regulate the immune response without severely suppressing the entire immune system. Using innovative biomaterials embedded with molecules that modify the immune response, Abdi is developing a gel substance to implant with the skin substitute that would eliminate the need to use systematic immunosuppressive drugs.
“The skin has a sophisticated immune system, so finding the optimal bio-ingredients that would be compatible when implanted with the skin substitute is the challenge. But if conducted successfully, the acceptance of the skin allograft without immunosuppressive drugs could be incredibly advantageous in reducing the risk of infection while improving the survival rate of severe burn patients,” said Abdi.
While Abdi’s strategy holds great potential, the project is a “high-risk, high-reward” idea. Funding is difficult to obtain during the early stages, but is necessary in order to gather data to best optimize the substance. Fortunately, with the help of the Brigham Health and Technology Innovation funding from the Shark Tank competition, Abdi is now about to screen outcomes of biomaterials with various scaffold models to identify which materials perform the best.
“It is important to view this project from an interdisciplinary perspective,” said Abdi. “When evaluating biomaterials, my perspective is very clinical, and so it is important to gather feedback from other disciplines to keep the composition of biomaterials simple.”
After amassing enough evidence in the laboratory setting, Abdi’s next step is to gather clinically relevant data, with the goal of translating these findings into clinical applications. He also plans to apply the data to a humanized mouse model (mice that carry functional human cells) to evaluate the survival of the skin by using the developed substance on a model more similar to human tissue.
Not only could this project directly improve outcomes of patients with severe burns, but the data gathered may also benefit Abdi’s other research in transplantation tolerance.
“If I am able to develop this form of localized immune modulation at the wound site, I would also be able to more widely apply it in the context of other organ transplants, such as the kidney. Therefore, the success of this project has many implications for advancing transplantation science,” said Abdi.
With an insightful mindset and a practical plan, Abdi’s innovative strategy could provide a new solution for trauma patients with severe burn injuries.