Blocking the skin’s response to physical stimuli can promote healing

Reducing the skin graft’s response to its physical environment may help improve healing and reduce scarring from major damage such as burns or explosive wounds, according to our recent study published in Science Translational Medicine.

Historically, injuries that cover massive areas of the body like burns to have high mortality rate. Over the past 50 years, progress has been made in wound care using techniques such as skin graft often allowed patients to survive. During this process, a thin layer of healthy skin is removed from the intact area of ​​the body and transplanted to cover the burn. Typically, these skin grafts are mesh or perforated to cover larger areas, much like a mesh fence takes up more space overall than a solid metal wall of the same weight.

However, a skin graft still leads to long-term problems. Grafts can shrink, shrink in size and become much denser and fuller scar tissue. If these skin cuts occur on the joints or face, they can restrict movement and eventually become crippled. The emergence of c scar tissues can also be unattractive to patients. The only currently available skin reduction remedy is remove the affected graft and replace it with a new one. But because skin contractions can form again, it can lead to a vicious circle if some patients undergo more than 60 repeat surgeries in a lifetime.

To figure out a way to prevent these skin cuts, my colleagues and I. at Stanford University applied skin grafts to surgically treated pigs, animals skin is most similar to human. We studied the genetic material of pig skin to determine which cell types are likely to promote healing and scarring, and found that skin grafts activated molecular pathways that control inflammation and mechanotransduction, the process by which cells sense and respond to physical stimuli. .

Next we included a drug called a focal adhesion kinase inhibitor in a hydrogel, a moist material that is insoluble in water, and apply it directly to the healing skin grafts. Because this drug suppresses the ability of the cell to respond to it physical environment, we hypothesized that this may disable inflammatory and mechanotransduction pathways. For 21 days, we found that drug-treated skin grafts reduced skin shrinkage and scarring, and improved healing compared to drug-free skin transplants.

We then looked at how well cells function in healing skin grafts, and found that cells treated with the drug looked more like healthy, uninjured cells than cells in untreated skin grafts. Cells in untreated skin grafts had highly activated inflammatory and mechanotransduction pathways, leading to increased scar formation.

Burns are some of the most destructive skin and posture damage a a serious burden on global public healthespecially in middle- and low-income countries. There are at least Annually 40,000 hospitalizations related to burn injuries in the United States, and an average of 200 annual appeals due to burns and skin diseases associated with burns in each of the country’s 128 burn centers. Scars from burns and skin grafts can cause mutilation, mobility impairment and psychological distress.

Ours drug therapy offers a way to reduce scarring and promote recovery without additional treatments. Hydrogels used by our treatment already widely used when caring for wounds. We believe ours drug can be easily incorporated with standard wound treatment at the clinic without additional workload for patients or physicians.

While our study suggests one way to prevent scarring after injury, little is known about how to effectively remove existing scars or reverse the scar formation process. In our future work, we hope to develop similar treatments to eliminate scars and help millions of Americans suffer from skin scars.

We are now preparing to test this therapy in clinical trials with patients.

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