A Burns & Trauma paper has reviewed strategies for treating hypertrophic scars. While scars are common when wounds heal, hypertrophic scarring is a skin condition characterized by deposits of excessive amounts of collagen. This results in a thick and often raised scar, but the underlying mechanisms of hypertrophic scar development are poorly understood. The researchers argue that we need long-term results in order to make decisions about using resection or radiation as a medical intervention. The drug botulinum toxin A (btxA) is widely used for cosmetic purposes, as well as treating headaches and other pain. It is also often used to treat hypertrophic scars.
They emphasize that while btxA appears to have some positive effect on scar prevention, researchers still haven't decided on the optimal concentration of the drug to treat scarring. It may depend on the size or severity of the wound. They conclude the drug is promising and worth investigating further. Future management possibilities for hypertrophic scar therapy include anti-angiogenesis therapy, which inhibits the development of new blood vessels, fat grafting, and stem cell therapy. There are several experimental investigations on the effectiveness of such therapies to reduce abnormal tissue formation.
Major risk factors for hypertrophic scar formation include gender, age, genetic predisposition, wound size and depth, anatomical site, and mechanical tension on the wound. Such scarring hinders normal function, and results in serious physical, psychological, and aesthetic problems for patients. It is widely accepted that the time to complete wound healing is the most important factor to predict the development of hypertrophic scars. Only one-third of wounds developed scarring tissue if healing occurred between 14 and 21 days. Some 78 percent of the sites resulted in serious scarring if the wound healed after 21 days.
What Is Skin Wound Healing?
Skin wound healing is a process that consists of three phases: inflammation, proliferation, and regeneration. Hypertrophic scar formation can occur as a result of an abnormality in these processes. The frequency of such scarring ranges from 40 to 94 percent following surgery and from 30 to 91 percent following a burn injury. In poorer countries, the incidence rate is greater reflecting the high rate of burn injuries. The established therapies for preventing serious skin scarring include pressure therapy, which has long been considered the mainstay non-invasive treatment for hypertrophic scarring.
It is widely used worldwide and its effectiveness has been established. It's suggested that it is more effective if pressure therapy is performed within two months after the initial injury. Other interventions include silicone, steroids, and laser therapy. While the effectiveness of silicone therapy has not been completely determined, the topical administration of steroids for burn injuries has been generally used and reported to be effective. There is consistent evidence that early laser intervention for the prevention would be beneficial in both the speed of scar reduction and the efficacy of therapeutic response.
Cutting out the tissue – known as resection – as well as radiation can often be used in addition to the primary therapies. Surgical approaches vary with the type of scar. Researchers involved with this paper argue that we need long-term results in order to make decisions about using resection or radiation as a medical intervention. The drug botulinum toxin A (btxA) is widely used for cosmetic purposes, as well as treating headaches and other pain. It is also often used to treat hypertrophic scars.
Turning Open Wounds Into Skin
Scientists at the Salk Institute have developed a technique to directly convert the cells in an open wound into new skin cells. The findings were recently published in the journal Nature. The approach relies on reprogramming the cells to a stem-cell-like state and could be useful for healing skin damage, countering the effects of aging and helping us to better understand skin cancer. Plastic surgery to treat large cutaneous ulcers, including those seen in people with severe burns, bedsores or chronic diseases such as diabetes, may someday be a thing of the past.
Juan Carlos Izpisua Belmonte, a Salk Professor, holder of the Roger Guillemin Chair and senior author of the paper, along with Salk Research Associate Masakazu Kurita, who has a background in plastic surgery, knew that a critical step in wound recovery was the migration or transplantation of basal keratinocytes into wounds. These stem-cell-like cells act as precursors to the different types of skin cells. But large, severe wounds that have lost multiple layers of skin no longer have any basal keratinocytes. And even as these wounds heal, the cells multiplying in the area are mainly involved in wound closure and inflammation, rather than rebuilding healthy skin. They wanted to directly convert these other cells into basal keratinocytes without ever taking them out of the body and set out to make skin where there was no skin to start with.
Growing Healthy Skin
The researchers compared the levels of different proteins of the two cell types - inflammation and keratinocytes - to get a sense of what they'd need to change to reprogram the cells' identities. They pinpointed 55 "reprogramming factors" - proteins and RNA molecules - that were potentially involved in defining the distinct identity of the basal keratinocytes. Through trial and error and further experiments on each potential reprogramming factor, they narrowed the list down to four factors that could mediate the conversion to basal keratinocytes.
Cutaneous ulcers – or wounds that can extend through multiple layers of the skin - are typically treated surgically, by transplanting existing skin to cover the wound. When the ulcer is especially large, it can be difficult for surgeons to graft enough skin. In these cases, researchers are able to isolate skin stem cells from a patient, grow them in the lab and transplant them back into the patient. Such a procedure requires an extensive amount of time, which may put the patient's life at risk and is sometimes not effective. When they topically treated skin ulcers on mice with the four factors, the ulcers grew healthy skin - known as epithelia - within 18 days. Over time, the epithelia expanded and connected to the surrounding skin, even in large ulcers. At three and six months later, the generated cells behaved like healthy skin cells in a number of molecular, genetic and cellular tests. The researchers are planning more studies to optimize the technique and begin testing it in additional ulcer models. "Before going to the clinic, we have to do more studies on the long-term safety of our approach and enhance the efficiency as much as possible," Kurita said.
"Our observations constitute an initial proof of principle for in vivo regeneration of an entire three-dimensional tissue like the skin, not just individual cell types as previously shown," added Belmonte. "This knowledge might not only be useful for enhancing skin repair but could also serve to guide in vivo regenerative strategies in other human pathological situations, as well as during aging, in which tissue repair is impaired."
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With over 30 years of writing and editing experience for newspapers, magazines and corporate communications, Kevin Kerfoot writes about natural health, nutrition, skincare and oral hygiene for Trusted Health Products’ natural health blog and newsletters.
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