Research reveals clues as to how molecule improves appearance of surgical scars

Surgical scars treated with a molecule called alphaCT1 have shown long-term improvement in appearance compared to control scars, according to multicenter, controlled phase II clinical trials – a finding that could help surgeons improve outcomes for patients. patients.

Today, a public-private research team led by Rob Gourdie, professor and director of the Center for Vascular and Heart Research at VTC’s Fralin Biomedical Research Institute, revealed clues as to why and how it improves the appearance of scars.

The study, which will be published in the August issue of Journal of the Federation of American Societies for Experimental Biology (FASEB), describes how the drug influences the behavior of collagen-producing cells called fibroblasts.

The findings reveal a previously unreported feature of scar formation and may help advance wound healing treatments for patients undergoing surgery.

Researchers analyzed the scars of 49 healthy volunteers in a randomized, double-blind phase I clinical study. Each volunteer had 5-millimeter skin punches biopsied from each of their internal biceps. The wound of one arm was treated with the alphaCT1 molecule in a gel, and the other received a non-drug control gel. The wounds healed for 29 days, after which the scars were again photographed and biopsied.

Under a microscope, untreated scar collagen – a protein produced by cells called fibroblasts – has formed parallel bands, making the tissue less flexible. In contrast, the scars applied with the drug had a collagen matrix resembling uninjured 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 observe in real time how the drug influenced cell activity. They found that the presence of the molecule caused the fibroblasts to stretch like a rubber band, then reshape them and change direction.

“We call it the fibroblast dance,” said Gourdie, who is also the Commonwealth Research Commercialization Fund’s distinguished researcher in cardiac restorative medicine and professor of biomedical engineering and mechanics at the Virginia Tech College of Engineering.

This unusual behavior of fibroblasts in the treated tissue appears to have a positive effect on scar formation, Gourdie explains.

In uninjured skin, collagen becomes entangled, allowing tissue to move and stretch in all directions. Changes in the direction of fibroblasts appear to influence the formation of the collagen matrix during healing. “

Rob Gourdie, Professor and Director of the Center for Vascular and Heart Research, Fralin Biomedical Research Institute, VTC

Over 300 million surgeries are performed in the United States each year, often resulting in visible scars on patients. Methods for reducing scars after operations are being researched.

“This is one of the most exciting basic scientific research into wound healing that I have seen in a long time,” said Kurtis Moyer, chief 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 collaborated with the Gourdie lab on wound healing research for 20 years.

“This is really promising and could potentially revolutionize what we do in plastic surgery,” Moyer said.

AlphaCT1 influences wound healing by temporarily disrupting the cell signaling functions of connexin 43, a gap junction channel protein.

Gourdie and his lab invented the molecule and discovered its useful effects on wound healing with his former postdoctoral associate, Gautam Ghatnekar, ten years ago. Together, they formed a biopharmaceutical company, FirstString Research Inc., to commercialize alphaCT1.

The molecule is currently being evaluated in phase III clinical trials in patients who have undergone bilateral breast surgery.

“These results confirm that the drug mechanism is working as we expected,” said Ghatnekar, President and CEO of FirstString.

The company has closed $ 55 million Series B, C and D funding since 2018 and is evaluating the use of the drug in a variety of applications, including surgical wound healing, chronic wound healing, radiotherapy wound healing. and corneal tissue repair.

“We are changing the way the human body responds to injury by shifting the balance from scar healing to regenerative healing. The medical applications of our technology are very wide,” said Ghatnekar.

Source:

Journal reference:

Montgomery, J., et al. (2021) Connexin 43 αCT1 carboxyl terminal mimetic peptide induces the differentiation of a collagen scar matrix in humans resembling uninjured skin. FASEB review. doi.org/10.1096/fj.20201881R.


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