Surgery saves and improves lives. However, one of the downsides is scarring. Those who have undergone open-heart surgery, for instance, often have very large, prominent scars. Past research has demonstrated that a person’s level of scarring often has to do with the location of the injury or incision. More specifically, cuts or incisions on skin where there is more tension, such as across joints or on the chest where breathing causes constant strain, are more prone to unsightly scarring.

Thanks to new research conducted by Oregon Health & Science University in collaboration with Stanford, scientists now have a better understand of why this is the case. The research also suggests promising new methods for reducing scarring following surgery or injuries. The results are published online in the journal Nature Medicine and will appear in a future printed edition of the journal.

Through both human and animal studies, the researchers studied the molecular pathways underlying hypertrophic scar formation. Their focus: to find the genes activated when a wound is under tension. This analysis led researchers to focal adhesion kinase (FAK), a protein involved in converting mechanical signals into biologic responses. The researchers then studied the impact on healing when FAK signaling was specifically blocked. This was done in two methods: 1.) Through the use of genetic technology to specifically delete FAK in skin fibroblasts and, 2.) through the use of a small molecule inhibitor of FAK. In both cases, tension-induced scarring was significantly reduced.

Victor W. Wong, M.D., the lead author of this paper and a general surgery resident in the OHSU School of Medicine, conducted the research at Stanford University under surgeons Geoffrey Gurtner and Michael Longaker, and in collaboration with Anna Kuang, M.D., head of pediatric plastic and craniofacial surgery at OHSU. His hope is that the conclusions will provide a more comprehensive understanding of wound repair and lead to new treatments for hypertrophic scarring.

“We believe that this information can result in novel devices and medications that help reduce scarring,” said Wong. “This would be particularly beneficial for burn and injury patients. Previous research on scarring has focused largely on cytokines, but the wound environment is much more complex. Mechanical forces play a major role in all biologic processes including wound healing and scarring. By understanding our biologic mechanisms to sense and respond to physical force, we can hopefully develop more targeted therapies that prevent excess scarring without impairing normal wound healing. More broadly, this study highlights the potential to manipulate mechanical cues – through device or pharmaceutical approaches - to mitigate disease processes such as inflammation and scarring.

The Oak Foundation, the Hagey Family Endowed Fund in Stem Cell Research and Regenerative Medicine and a United States Armed Forces Institute of Regenerative Medicine grant supported this work.