Thomas Morrow, MD
Fish skin for wound healing doesn’t need harsh processing. Source: Lamed GmbH

Your skin is an amazing organ, possessing a strong mesh like matrix that is both flexible and elastic. It contains numerous layers that protect the underlying tissue from trauma and invasion by pathogens. But once this barrier is breached, the body starts a complex process to mend the damage. The process of healing involves recreating the strong elastic mesh of the skin, populating it with cells that can reproduce the dermal and epidermal layers, and growing new blood vessels into the damaged area. The repair work is really something of a race between the production of molecules that aid in the healing and the degradation of these same molecules by inflammatory processes, infection, localized recurrent trauma (even minor abrasion), lack of oxygen, and shortages in essential nutrients. The winner is highly dependent upon the blood supply and the size of the area injured.

If you are reading this column, you have certainly lived long enough to experience some kind of laceration. If I asked you what is the relative healing time for identical wounds on the face and foot, you’d be right if you said the foot would heal more slowly. This observable fact of life is based on the relative blood supplies of these areas. Blood is the body’s liquid health care provider. It brings all of the substances to bear that promote healing, including oxygen, nutrients, cells needed to repair the injury, as well as those needed to fight infections, including white blood cells and antibodies. The face is more amply supplied with blood vessels than the feet, so it heals faster.

The healing power of blood

The distinct difference in the blood supply in the distal extremities becomes even more important for people as they develop micro- or macrovascular disease caused by any number of diseases but most commonly atherosclerosis and diabetes (with obesity being a predicate condition for many).

Serious problems may start with what seems like a small, even trivial, injury. In people with vascular disease, those small wounds can become chronic because the competition between healing and the degradation of its agents in which healing usually prevails instead goes to degradation. In a small portion of patients, the doctors are forced to treat these chronic wounds with amputation. They remove as little tissue as possible to get to the area of the extremity that has a viable vascular supply.

Chronic wounds are common, and both the incidence and prevalence of them is expected to increase because of the growing number of people around the world with diabetes. And the sad fact of the matter is that between 2% and 10% of people with diabetes develop a foot ulcer and more than half of those who experience recurrent foot ulcers will need an amputation of some kind.

Regardless of whether an amputation has occurred, the wound needs to be tipped back into the healing process. Early attempts to use tissue from mammals for this purpose were problematic. Mammals can carry pathogens common to man, so any implanted tissue needs to be rather harshly processed to destroy bacteria, viruses, and prions (a family of infectious agents that cause a number of illnesses such as mad cow disease). The processing removes many of the natural components necessary for viable human wound healing.

Artificial products have also been tried and are on the market, but unmet need remains. Now an Icelandic company called Kerecis has come up with a viable substitute to the artificial and mammalian tissue products that is made from fish skin, more specifically cod fish skin.

Fishy but fine

Fish skin has a number of properties that make it a good candidate for wound healing. The structure is similar to human skin. Harsh processing isn’t necessary because there are no common pathogens between fish and humans. Perhaps most importantly, fish skin skews the contest between healing and the biodegradation of healing molecules toward the healing side. Fish skin is very high in omega-3 fatty acids, compounds that promote healing. And cod evokes virtually no inflammatory or immune response in humans. It’s also a very familiar fish and has been the subject of numerous studies as various components of cod have been used as human food for centuries.

Flaps of scaly skin being applied to wounds—that may be the image that comes to mind when people hear or read about Kerecis’s product. The reality is quite different. The fish skin goes through a complex process to remove all fish cells, rendering it into an “acellular dermal matrix,” which is strong, non-reactive but still retains the high levels of omega-3 fatty acids.

Kerecis’s product, which it is selling as Kerecis Omega3, received FDA approval earlier this year for the following indications: reinforcement of staple lines during bariatric surgical procedures; colorectal and colon surgical procedures; gastric, small bowel, and mesentery procedures; lung and bronchus resections; and repair of skin lesions.

The company got its go-ahead through the FDA’s looser predicate device process. Still, the fish skin product has been studied quite a lot, in both the lab and in humans, although in many cases the research has been done by researchers who have done work for Kerecis in some capacity or another.

A 2015 study showed acellular fish skin was found to be porous and demonstrated proteins similar to human collagens. The processing of the fish skin is designed to remove major antigenic components, and studies have shown that it does not elicit a significant effect on the secretion of IL-10, IL-12p40, IL-6, or TNF-alpha from monocytes or macrophages. Other research has shown that the fish skin material ramps up angiogenesis (the creation of small blood vessels) in a standard animal model called the chick CAM assay.

Laboratory investigation has shown that the graft material contained fat-soluble vitamins, and phospholipids as well as omega-3s.

The fish skin product has been tested in several clinical studies. One study involved 81 volunteers, each of whom agreed to have two identical adjacent punch wounds made on the proximal anterolateral aspect of their nondominant arm. One wound was covered with porcine small-intestine product, the other with Kerecis Omega3. The wound treated with the fish product healed significantly faster. Another notable small study involved seven patients who had undergone amputations because of diabetic vascular disease that resulted in “insufficient soft-tissue coverage with exposed bony segments.” Translation: There isn’t enough viable skin to cover the bone at the end of the amputation. Kerecis’s product was applied after surgical debridement to cover the gap. The results showed that patients took fewer painkillers after the fish skin product was applied. Prompt healing was demonstrated in other studies.

We humans have been consuming fish since time immemorial when we first figured out how to catch them. Numerous studies have shown that fish is important to a healthful diet. As a child I remember being lined up with my siblings and literally “forced” to take cod liver fish oil as a nutritional supplement. Now, it seems, we have figured out another use of that same fish that speeds healing and could be especially helpful in the treatment of amputations, diabetic foot ulcers, and other surgical wounds…all without the aftertaste!

Thomas Morrow, MD, is the chief medical officer of Next IT. He has been the founding medical director of five HMOs and a disease management company, a medical director at Genentech, and president of the National Association of Managed Care Physicians. You can contact him at thomasmorrowmd@hotmail.com.

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