Virginia Tech scientists discover how a molecule improves the appearance of surgical scars
Surgical scars treated with a molecule called alphaCT1 showed long-term improvement in appearance compared to control scars, according to multicenter, controlled, Phase II clinical trials – a finding that could help surgeons improve patient outcomes.
A public-private research team led by Rob Gourdie, Professor and director of Center for Vascular and Heart Research In the Fralin Biomedical Research Institute at the VTC, has revealed clues as to why and how it improves the appearance of scars.
The study published in the August issue of Federation of American Societies for Experimental Biology (FASEB) Journal, describes how the drug affects the behavior of collagen-producing cells, the fibroblasts.
The results reveal a previously unreported feature of scarring and could help advance wound healing in patients undergoing surgical procedures.
The researchers analyzed scars from 49 healthy volunteers in a randomized, double-blind Phase I clinical trial. Each volunteer was given 5 millimeter skin biopsies from each of their internal biceps. The wound in one arm was treated with the alphaCT1 molecule in a gel, the other received a non-drug control gel. The wounds healed for 29 days, after which the scars were photographed and biopsied again.
Under the microscope, the untreated scars’ collagen – a protein made by cells called fibroblasts – formed parallel strips that made the tissue less pliable. In contrast, scars applied with the drug had a collagen matrix that resembled unwounded skin. Related experiments were repeated using guinea pig and rat models and gave similar results.
The researchers also analyzed human skin cells grown in a dish to see how the drug affects cell activity in real time. They discovered that the presence of the molecule caused the fibroblasts to expand like a rubber band, then snap back into shape and change direction.
“We call it the Fibroblast Dance,” said Gourdie, who is also an Eminent Scholar in Heart Reparative Medicine Research at the Commonwealth Research Commercialization Fund and a professor of biomedical engineering and mechanics at Virginia Tech’s College of Engineering.
This unusual behavior of the fibroblasts in the treated tissue appears to have a positive effect on scarring, says Gourdie.
“The collagen is interwoven in the unwounded skin so that the tissue can move and stretch in all directions. The changes in direction of the fibroblasts seem to affect the formation of the collagen matrix during scarring, ”said Gourdie.
More than 300 million surgeries are performed in the United States each year, often leaving noticeable scarring in patients. We are looking for methods to reduce scarring after operations.
“This is one of the most exciting basic wound healing research I’ve seen in a long time,” said Kurtis Moyer, chief physician of plastic and reconstructive surgery at the Carilion Clinic and professor of surgery at the Virginia Tech Carilion School of Medicine. Moyer was not involved in the study, but has worked with the Gourdie Laboratory on wound healing research for 20 years.
“This is promising and could potentially revolutionize what we do in plastic surgery,” said Moyer.
AlphaCT1 influences wound healing by temporarily disrupting the cell signaling functions of connexin 43, a gap junction channel protein.
Gourdie and his laboratory invented the molecule and discovered its beneficial effects on wound healing with former postdoctoral fellow Gautam Ghatnekar a decade ago. Together they founded a biopharmaceutical company, FirstString Research Inc., to bring alphaCT1 to market.
The molecule is currently being evaluated in phase III clinical trials in patients with bilateral breast surgery.
“These results confirm that the drug’s mechanism works as we envisioned it,” said Ghatnekar, President and Chief Executive Officer of FirstString.
The company has funded $ 55 million in Series B, C, and D since 2018 and is evaluating the drug’s use in a variety of applications including surgical wound healing, chronic wound healing, radiation therapy wound healing, and corneal tissue repair.
“We’re changing the human body’s response to injury by shifting the balance from healing through scarring to healing through regeneration. The medical applications of our technology are wide-ranging, ”said Ghatnekar.
Gourdie and Ghatnekar were involved in the study by lead author Jade Montgomery, a former PhD student in Gourdie’s laboratory at the Fralin Biomedical Research Institute and the Department of Biomedical Engineering and Mechanics at Virginia Tech. William Richardson, Assistant Professor of Bioengineering at Clemson University; Spencer Marsh, postdoc in Gourdie’s lab; Matthew Rhett, a research fellow at the Medical University of South Carolina at the time of the study; Francis Bustos, a former medical student; Katherine Degen, a former PhD student in Gourdie’s laboratory at the Fralin Biomedical Research Institute and Virginia Tech – Wake Forest School of Biomedical Engineering and Sciences; Christina Grek, Senior Director for Research and Development at FirstString; Jane Jourdan, Gourdie’s laboratory manager; and Jeffrey Holmes, dean of engineering at the University of Alabama.
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