Autologous Regeneration in Burn Injured Patients

I think we often remove too much tissue just to be safe. If we could take less … and let the wound heal in on its own, the patient wouldn’t have to have a whole other wound.

– Dr. Angela Gibson

At a Glance

Each year, around 11 million people worldwide sustain burn injuries severe enough to require medical attention. One year in Wisconsin contributes 61 fatalities and over 600 hospitalizations related to burn injuries to the worldwide total. Burn survivors can experience lifelong pain, scarring, and infection from burns as well as from the surgery needed to heal the wounds. As such, there is a significant need to develop new treatment strategies. This work aims to understand how healing can be accomplished without grafting healthy skin from the patient’s body.

The research team met the overall goals of this project, which included developing and characterizing an ex vivo (outside of an organism) human burn injury model, including instrumentation to generate consistent and reliable thermal injury identification of the natural variation in human skin, and the ability of the tissue to recover in culture.

The Challenge

In Wisconsin, 61 fatalities and more than 600 hospitalizations related to burn injuries occurred in one year. Current treatment of deep burn wounds requires the surgical removal of injured tissue until viable tissue is visible. This treatment requires a method called tangential excision that prepares the wound bed for skin grafting. However, using visual assessment isn’t a precise technique, and 40% of excised burned tissue contains visible dermis. Burn survivors can experience lifelong pain, scarring, and infection from the burns as well as from the surgery needed to heal the wounds. Thus, there is an urgent need to develop new methods for treating serious burns.

Project Goals

The goal of this project was to reduce the pain and suffering of burn patients by understanding how wound healing can be accomplished without grafting healthy skin from a different part of the patient’s body. The proposed work aimed to yield insights into wound healing processes to help people who suffer burn injuries in Wisconsin and beyond.

Results

The research team met the overall goals of this project, which included developing and characterizing an ex vivo human burn injury model. They were able to establish instrumentation to generate consistent and reliable thermal injury, identify the natural variation in human skin, and understand the ability of the tissue to recover in culture. Additionally, the researchers completed the first phase of a humanized mouse model of human wounds. They characterized the time course after grafting human skin until recovery of the tissue for further experimentation. These details provided the foundation for using these models to mimic acute and chronic wounds for future interventional studies and enhanced collaborations across the University of Wisconsin and the country.

The development of these models has led to two new collaborations across campus. Dr. Lindsay Kalan, an Assistant Professor of Microbiology, and Dr. Gibson will investigate the effects of thermal injury on biofilm formation on human skin. The second collaboration is with Dr. Xudong Wang, a professor of Engineering, and was awarded a UW2020 grant through the Wisconsin Alumni Research Foundation (WARF).

This project had great success in publishing and disseminating its findings, including peer-reviewed poster sessions, peer-reviewed oral presentations, peer-reviewed publications, invited presentations, and social media coverage. Presentations at University of Wisconsin Department of Surgery 10th Annual Research Summit and 15th Annual Academic Surgical Congress were among the ten presentations given from the research team.

Looking to the Future

Long term plans for sustainability of this project include application for federal funding through R01 and P50 mechanisms. As a bridge to that funding, Dr. Gibson has been awarded a UW 2020 grant as co-co-principal investigator for the project Nanogenerator-Driven Self-Activated Electrical Stimulation for Enhanced Wound Healing utilizing the human skin models developed and optimized with this funding. This funding will define the mechanism of nanogenerated electrical stimulation on wound healing in human skin. Finally, as a continuation of the thermal injury modeling work in collaboration with labs across the country who specialize in pig models, the research team will use these models to evaluate the similarity of the pig and human models.

Lasting Impact

The newly-established ex vivo and in vivo human skin models for wound healing can be adapted to various environments. These outcomes are beneficial to the academic community at UW and the wound healing research community at large as a preclinical model. The researchers have multiple existing and new collaborations that will benefit from the further characterization of these models to allow future understanding of human wound healing. The long-term potential outcomes include the increase in ability to translate wound healing research, as well as additional collaborations across campus, state and the country. Ultimately, with the cross-disciplinary collaborations that are developed as a result of these studies, the researchers will be well-poised to submit a program project (P50) grant for federal funding.