In a groundbreaking study, a research team has found that chronic wounds in preclinical models were able to heal with normal, scar-free skin following treatment with an acellular product discovered at Mayo Clinic.
Derived from platelets, the purified exosomal product, known as ‘PEP’, was used to deliver healing messages into cells of preclinical animal models of ischemic wounds triggering wound healing and skin regeneration. The team documented the restoration of skin integrity, hair follicles, sweat glands, skin oils, and normal hydration. Ischemic wounds occur when arteries are clogged or blocked, preventing nutrients and oxygen from reaching the skin to trigger repair.
The research is supported by Mayo Clinic’s Center for Regenerative Medicine, and the study has been published in Theranostics.
Chronic wound healing
Chronic ischemic wounds are common in people with conditions such as diabetes, pressure ulcers, hardening of arteries, traumatic injury, or side effects of radiation therapy.
Currently, treatments for these wounds include wound dressing, topical gels, and surgery, however, they often cannot fully close the wound and when the condition progresses, nonhealing wounds lead to limb amputation.
This purified exosomal product is an extracellular vesicle that delivers cargo from one cell to another, targeting exact tissues in need of repair. The technology for the device is formulated as a dry powder to enable long-term storage at room temperature and, in the operating room or at the bedside, the powder is mixed with a hydrogel solution on-site and can be applied directly to the wound. Unlike cellular products, it does not have to be sent to an outside laboratory to be cultured and scaled.
Steven Moran, M.D., a Mayo Clinic plastic surgeon and senior co-author on the study, said: “This paper documents that PEP, an off-the-shelf, room-temperature-stable exosome, is capable of healing wounds that are depleted of adequate blood supply. Wounds healed with only a single application of exosome.
“I was surprised that this product regenerated healthy skin with normal biomechanical properties — not scar tissue. As this technology is now scaled and biomanufactured for clinical applications, it creates the potential for huge advancement in medical science and the field of plastic surgery.”
“What we see with this technology is not just that the wound is closed, but also that the blood supply to the tissue is restored. Our effort culminating in the development of this exosomal technology was to create a therapy that can be offered to all patients in need through elimination of logistical limitations often seen with more traditional regenerative therapy,” says Atta Behfar, M.D., Ph.D., deputy director of Translation, Mayo Clinic’s Center for Regenerative Medicine and senior author.
Exosomal products vs hydrogel
For the research, the team replicated wounds with low blood supply in large animal models.
They treated some of the wounds with the purified exosomal product and compared them to wounds that were treated with the hydrogel alone, finding that the exosomal treated wounds were able to heal with skin restored to its normal architecture.
“Our research hopes to answer whether this can be a new healing solution for patients suffering with nonhealing chronic wounds,” said Dr Behfar, director of the Mayo Clinic Van Cleve Cardiac Regenerative Medicine Program where the purified exosomal product was discovered.
Ao Shi, Ph.D., a student in the Regenerative Sciences Training Program in Mayo Clinic Graduate School of Biomedical Sciences and first author, added: “We found that this exosome therapy has the ability to enhance regeneration of blood vessels in damaged tissues. Without treatment, chronic ischemic wounds grow larger and more problematic.”
A first-in-class clinical trial will now be launched based on the findings.