How electrical stimulation promotes healing

Scientists have known for decades that electrical stimulation promotes the healing of chronic wounds, such as diabetic ulcers and pressure ulcers, but the way this happens has been a mystery, until now.

"Electrical stimulation forces cells to promote migration to the wound center," said Assistant Professor Mark Messerli of the Department of Biology and Microbiology at the State University of South Dakota. College of Natural Sciences. Messerli and his team have developed a tool that predicts the course of cell migration and alignment. This research appears in the June issue of the Journal of Theoretical Biology.

In the clinic, electrical stimulation can accelerate the healing of chronic wounds, defined as skin lesions that do not heal within 30 days, and have been used to treat wounds that have existed for a year, Messerli explained. In addition to healing wounds, electrical stimulation promotes fixation of skin grafts, improving results for burns.

However, there is no standardized treatment, noted Messerli:

A patient may enter a different clinic and receive a totally different treatment for the same wound. We can not standardize or optimize treatments without knowing how electrical stimulation promotes healing. "

Chronic wounds of the skin tend to affect the elderly and diabetic patients. Nearly 15% of Medicare beneficiaries suffer from chronic wounds, resulting in estimated health care costs of $ 28.1 to $ 31.7 billion a year, according to a 2017 study based on a Medicare dataset As more and more baby boomers reach retirement age, the number of patients and health care costs will continue to increase.

In addition, learning how electricity boosts the healing of wounds can provide some of the knowledge necessary for the growth of organs. "The healing of wounds leads us to tissue engineering," said Messerli. "It's like building a brick wall." The bricks must be carefully aligned and spaced out of mortar to form a structurally sound wall.Also, the cells must be carefully aligned and badembled so that a human organ can working properly."

The study was funded by the Eugene and Millicent Bell Tissue Engineering Scholarship Fund and funding from the US Department of Agriculture Hatch through the South Dakota Agricultural Experiment Station at SDSU. An SDSU doctoral student and a master's student worked on the project.

How electrical stimulation heals wounds

Electrical stimulation is used clinically to activate neurons, muscles and endocrine cells, but they are electrically excitable cells. Skin cells are not considered electrically excitable. So, how can a skin cell detect weaker electric fields than those used to stimulate neurons or muscle cells? "

Mark Messerli, Assistant Professor, South Dakota State University

Scientists know that very weak electric fields polarize cells and cause them to migrate or grow towards one of the electrical poles, he explained. "The function of tissues and organs is based on cell polarity, we need this cellular organization to have a functional organ."

Mammals, including humans, have what Messerli calls "an endogenous electric field on the skin". When the skin is broken, there is an electric field perpendicular to the edge of the wound, which directs the cells towards the middle of the wound. However, this electric potential decreases with age.

"A weak electric field causes proteins to migrate to the surface of the cells towards the electrical poles depending on their size and charge," he said. "The electric field across the cell membrane is greater than one million volts per meter, but epidermal cells can detect electric fields just under 10 volts per meter, nearly 100,000 times lower."

The researchers used a combination of mathematical modeling tools, fluorescence imaging, and bioinformatic tools to develop a model that predicts the mode of redistribution of these proteins in the plasma membrane. "About 30% of the proteins in the human genome are in the plasma membrane, but up to now, fewer than 10 proteins have been badociated with electrically induced cell polarity," Messerli said.

After following the redistribution of a known protein, researchers used the model to predict the behavior of proteins identified by other research groups. "The model is about to predict the results of past experiences," he said. The predictive tool will help researchers identify the essential proteins for the electrical polarization of other cell types and to optimize wound repair with the help of electrical stimulation.

Advancing skin to the organs

By understanding how electrical stimulation promotes wound healing and the fixation of skin grafts, researchers are discovering how to rebuild tissues and organs. "We start with the skin, a two-dimensional organ," said Messerli, "but the goal is ultimately to use the patient's own cells to build three-dimensional organs that his body will not reject.

"Our work helps to lay the foundation for the polarization of cells of any tissue or organ and to unravel the mystery behind electrical therapies Just as the bricks of a wall are carefully organized, so must we do the same. with cells when building or rebuilding tissues and organs, "he concludes.