Louis Clark has had foot problems for six years.
"I was actually walking on a broken foot for about a year and a half, two years, because I felt nothing," said Louis Clark.
Nerve damage led to a charcot foot -- a condition where his bones weakened, collapsed and then split through the skin. The wound simply would not heal.
"Every day that that wound is open, you have a chance of infection setting in."
Mayo Clinic Doctor Steven Kavros says if a wound won't heal, amputation can be the next step. Now, by using one of the purest forms of collagen, he's seeing faster healing.
"Type 111 collagen is a special type of collagen that heals very quickly."
It's present in human fetuses but disappears after birth. This new material, called primatrix, is made from fetal cow tissue.
"This Primatrix is front-loaded with type 111 collagen, so it can stimulate not only wound healing, but wound healing in an organized fashion," said Steven Kavros, D.P.M., Podiatric Medicine and Surgery
at the Mayo Clinic in Rochester, MN.
It's activated in saline, then placed on the wound. Blood vessels integrate into it. It dissolves into the skin.
"What we are finding is that the wounds healed exponentially compared with the standard of care."
Instead of a wound healing in 32 weeks, the primatrix cuts healing time to less than 10 weeks. Louis says it changed his life.
"I would have had to have my foot amputated. There's no question about it."
Instead, his wound healed in six weeks.
"It's almost like a miracle, to be honest with you. I am very thankful. I really am."
THE FOLLOWING IS AN IN-DEPTH INTERVIEW WITH THE DOCTOR FROM THE STORY ABOVE:
Steven Kavros, DPM, from the Department of Orthopedic Surgery at Mayo Clinic in Rochester, MN, discusses a new product that is derived from fetal bovine dermal tissue to help chronic wounds heal faster.
What is your degree?
Dr. Steven Kavros: I’m a podiatrist, DPM: Doctor of Podiatric Medicine.
Ok and we say Mayo clinic?
Dr. Steven Kavros: Mayo Clinic in Rochester, Minnesota
How big of a problem are foot wounds and wounds that don’t heal in diabetics?
Dr. Steven Kavros: Foot ulcerations are a major problem for the diabetic and the patients at risk with diabetes neuropathy. Both patient populations are at a high risk, at some time in their life a diabetic will have a wound, a blister that can lead to a wound. It’s been estimated right now, that within the country there’s about 24 million diabetics and approximately 10 to 15% of these diabetics will have a wound that could either heal quickly or can go onto what’s called a chronic non-healing wound that has many other adverse opportunities for their health.
Can these wounds start as something benign?
Dr. Steven Kavros: They typically start with what’s called sheer, and that’s how we form a blister, it’s a rubbing and it will probably take place from rubbing in their shoe, they form a blister which goes to a full thickness wound and the problem is that the basic diabetic population once they develop a little nerve ending damage called sensory peripheral neuropathy, they don’t feel the shoe, that don’t feel a pebble or a stone in their shoe, they’ve developed a blister and they have what’s called an insensate foot, poor feeling they don’t know there’s a problem, after day or so it starts to fester become infected and then they start to see drainage, they might smell some odor a family member might see some redness and some swelling, some streaking going up their foot indicating infection.
If you have diabetes and you want to prevent this, is it simply about keeping your blood sugar under control or do you see too who have blood sugars in good control that get these or is that just very unlikely
Dr. Steven Kavros: Well obviously good diabetic control is essential they have to try to maintain good blood level control and that is part of the diabetic process. When I trained the patient was pounded to have good blood sugar control. Today not only is it important to have your blood sugars controlled but there are other cardio vascular risk factors, cholesterol, triglycerides and so on because the adverse effects of the blood sugar cause a myriad of other problems which is a major problem with healing wounds and also with their morbidity and their general health.
How do these wounds impact one’s life?
Dr. Steven Kavros: Well there’s a huge impact, if they are younger individual, for example say you’re a type one diabetic and you develop diabetes when you are 7 years old, by the time 20 years passes, you have had diabetes for quite a period of time, at that period of time in your life, if you are 27 years old, hopefully you are gainfully employed, if you have a wound that doesn’t heal it can affect you in the work place, very significantly, loss of income, infection, hospitalization all very costly.
Do you see these equally in type twos and type ones?
Dr. Steven Kavros: Well there is a high percentage of patients we see with type 2 diabetes, typically type 2 diabetes starts later in life. Again years ago, 20- 25 years ago, the average type 2 diabetic we might see in their 5th or 6th decade of life, today with changes in diet with obesity and things of that nature the type 2 diabetic is starting much earlier. Inactivity, things that change their lifestyle and young people in their teens in their early 20’s and developing type 2 diabetes instead of developing it 30 years later they are so much earlier, the downstream effects of that are much more significant because their neuropathy their circulation changes will take place at an earlier stage, their kidney changes, their eye changes all the things that diabetes effects, will start earlier in life, so instead of seeing these patients in their 50’s, 60’s, 70’s we’re starting to see them much earlier.
So what is the new product that you are studying?
Dr. Steven Kavros: The clinical trial is centered on patients who have poor wound healing and a wound that doesn’t heal within 4 weeks’ time or a month is termed a chronic wound if you have a wound that starts in the beginning of the month and heals in that month, it’s an acute wound if it goes past that calendar month, it’s termed a chronic wound, the diabetic and the patient with neuropathy have these wounds that are typically are chronic non healing wounds which there are many factors that go into that prognicity, too much pressure of weight bearing a bio burden or bacteria stuck on the surface of the wound inhibits wound healing, poor nutrition can inhibit wound healing poor vascularity poor circulation can do it there’s many ,many factors and it’s not one it’s totally a compendium of things that take place, so when wounds don’t heal they have other issues for example a fracture dislocation called Charcot joint, the Charcot joint can change the attitude and architecture of the joint significantly where they bear weight where mother nature never really intended them to bear weight, we want to close those wounds as quickly as possible so they don’t develop soft tissue or bone infection so they close the wound and get them to a state where they can have a reconstruction so that they can relieve the pressure that they should not have, so they don’t have recurrent ulcerations and the main effect is prevent a non-traumatic lower extremity amputation.
What is it that you are studying?
Dr. Steven Kavros: This material is called Primatrix it is a fetal bovine dermal replacement scaffold, in laymen's terms its collagen which is the building blocks of our soft tissue taken from a cow that hasn’t been born, a fetus and it is dry and It has special properties that we all have in-utero. Our collagen or that soft tissue building block is either type one or type 3. Type one collagen is the collagen that we all possess as adults, this product also has type collagen, which is only typically found in-utero. Type 3 collagen heals wounds very quickly. We know that in-utero if a child, they develop fingernails and toenails, if they scratch themselves they form a wound on their skin that fetus heals and you’ll never see a scar why? Because the type 3 collagen is a special type of collagen that heals very quickly, This Primatrix is front loaded with type 3 collagen so it can stimulate not only wound healing but wound healing in an organized fashion.
It looks like a flat white piece of mesh almost?
Dr. Steven Kavros: Exactly it’s a dried piece of the inner material from our connective tissue called collagen, it has little fenestrations or little cuts in it, we activate it with saline, which is our bodies normal .9% saltwater solution that encompasses most of our body weight anyway and we activate that, we make sure the wound is very clean and we do certain things to ensure cleanliness of the wound and then we out this Primatrix directly on the vascular wound, we live it there for a week and we change the dressing and then this Primatrix breaks down incorporates into the normal wound bed. Blood vessels come up and integrate into it, the dermis which is the soft tissue beneath our skin itself that has the blood and the nerve endings integrate into this dermal replacement scaffold it fills in the wound and then the skin cells grow over the top.
So this is not something that is removed?
Dr. Steven Kavros: No this stays and actually integrates into their wound.
And eventually dissolves as the wound heals?
Dr. Steven Kavros: yeah you can say dissolves because it integrates into your normal dermis and we’ve got very clear histological or cell microscopic forms of how this integrates into our normal human tissue and it basically fills in our normal human tissue, the dermis fills into this and grows new skin on top of it.
How does it go from the cow fetus to looking like that?
Dr. Steven Kavros: Well that’s the biochemical and the process that the company called TEI Biosciences does. They extract the fetal bovine, fetal cow collagen and through the lab they cleanse it synthesize it and put it into the sheet form.
Ok, so that’s the scaffold
Dr. Steven Kavros: That’s the scaffold that we apply to the human patient.
So tell me what your research has shown
Dr. Steven Kavros: Well the current clinical trial is the first attempt to differentiate normal would healing in the diabetic wounds, typically with or without Charcot, but it’s a patient that has neuropathy with or without diabetes, because that neuropathic endpoint is similar and what we are finding is that the wounds heal exponentially compared to the standard of care. In a typical neuropathic wound, first of all there really isn’t a typical because they could be under a metatarsal head in the forefoot it could be on the side of the foot with the Charcot, on the bottom of the heel even on the top of the foot. But the wounds heal anywhere from 12 to 14 weeks all the way up to about 28 to 32 weeks, depending on the size of the wound and the location and what I found in the clinical trial that is going on presently, is I’ve taken those wounds that typically can go anywhere from 12 to 32 weeks and healed them in about a third of the time. But we still adhere to the same principles of wound healing you have to offload them to take the pressure off, you have to have a wound bed that’s very clean, and we do certain things to ensure that we use low frequency ultrasound, it kills bacteria, we have to make sure that they have a viable wound bed that’s nice and red and pink to accept in, you can’t put it on something that is devitalized it has to have the right parameters in order to work. If you follow the guidelines of good wound healing this technique works.
So it heals faster and is it across the board, most people heal faster?
Dr. Steven Kavros: Yes, I mean everybody has a different rate, certain people are going to be a little bit slower than others but again if you look at the literature for neuropathic wounds, with or without diabetes it’s dependent upon the size of the wound, the location and the pressure that is born under that, if you can remove some of those things, the wound will heal quicker.
So it doesn’t necessarily heal better, but faster?
Dr. Steven Kavros: With the Primatrix, it heals faster and the reason we want it to heal faster is really pretty basic. Every day that that wound is open you have a chance of infection setting in we can handle the soft tissue infection pretty standard with antibiotics, once the infection gets to the bone, it’s totally different ball game, you have to débride bone, amputate possibly in order to heal that, antibiotics do not typically heal infected bone you have to get rid of the dead bone by definition of osteomyelitis bone is dead. The antibiotics that we take through the veins or even though the mouth can’t get to the sight of the dead bone; therefore you have to get rid of it.
So this seems like there would be no doubt that this would reduce amputations.
Dr. Steven Kavros: That’s our goal, our goal is to reduce non traumatic lower extremity amputations by getting wound healing to be extradited so they can either get into their right type of shoe with the insert to offload them, the right type of brace to off load them or get them to the path that they can get the reconstructive procedure by one of our foot and ankle surgeons that can realign the malposition of their foot and that will hopefully decrease the lower extremity amputation.
How is this product different from other things being studied or used, rather than just the standard of care?
Dr. Steven Kavros: Well this one has again type 3 collagen and most of the other ones do not. There are other products on the market that I still continue to use that are human tissue or other allograph type of tissue from an animal, we have products from horse, we have products from pigs, they all have their benefits, so this is just one of the newer products that’s available to us.
And the type 3 is it simply because it’s from a fetus?
Dr. Steven Kavros: No type 3 collagen is present in any animal in-utero, it’s present in a human, and it’s present in a pig, in a cow, in a horse, sheep it doesn’t matter. Once we come into the world that type 3 collagen goes away. Now there are stem cells that still carry the type 3 collagen, we just don’t have the technology yet to harvest that to put it into wound, to generate that new embryonic type of wound healing.
I assume that there are people who are trying to figure it out right?
Dr. Steven Kavros: absolutely.
How significant is this, what could this mean for patients to heal that much faster?
Dr. Steven Kavros: well the significance again is, if you can take a wound and instead of healing it in 30- 32 weeks and do it in 8 to 10 weeks the chance of infection is a lot less, the chance of getting them further along in their compendium of care, whether it is a reconstructive or we have patients also that are diabetics that have end stage renal disease, they are waiting for a kidney transplant. You can’t have a transplant, a kidney, pancreas type of transplant if they have an open wound because the chance of infection because of rejection of the kidney or the pancreas. So its multi factorial, we’re trying to get these patients healed as quickly as possible so their other major medical needs are met quickly efficiently and effectively.
What do you think of this?
Dr. Steven Kavros: Well I’ve had the good fortune of being able to use many different products over the past 15 years, 17 years, this one I think has a tremendous amount of potential. It’s rather easy to apply if you follow the principles, it doesn’t cause pain, patients are usually very compliant with this, you don’t have to take them to the operating room to do a procedure like this so they are very willing to be participatory in this and our infection rates are extremely low.
Are there side effect or any negatives, any risks that this poses?
Dr. Steven Kavros: Well the main contra indication is if somebody is allergic to beef, because this is a product that is derived from a cow. Now they are not ingesting it but you still have the antigens and you still have the chemical properties of beef, just as other things in orthopedics, for example we use injections in the knee called Synvisc materials used to supplement elasticity, if they are allergic to chicken or sulfur they can’t use it. So the only great limiting factors here are beef allergy.
Can you give me a recap of your patient Louis Clark?
Dr. Steven Kavros: Yes, Louis Clark, he has one of the more devastating problems with neuropathy called Charcot neuropathy, that’s a big mouthful of words but basically what it is, in a small select people with diabetes, with neuropathy or with neuropathic people with neuropathy, they can have this devastating fracture dislocation in their foot and ankle it’s typically a weight bearing joint, it can happen in the knee but the predominance part of a foot or ankle, they lose their architecture by a collapse. They have a phase where their autonomic nervous system, the part of our nervous system that we can’t control, unless you are the Dalai Lama or a yoga expert, you can’t control the flow of your blood. People with neuropathy, with or without diabetes have this autonomic dysfunction, they have minor trauma stepping off a curb, going down a stair, their foot swells up like a football, all the way up to their knee typically. They think they’ve had some type of vascular problem, deep vein thrombophlebitis and it’s not until they have an x-ray that we see this destruction of bone, their bones collapse they bear weight in places where they shouldn’t bear weight and after about 6 months their foot finally calms down and consolidates and they might have what’s called a rocker deformity on the bottom of their foot, where their arches collapse and now the weight is on an area on the sole of their foot , where most of us don’t bear weight, that rubs that forms an ulcer it can go very deep, cause a lot of infectious problems and Mr. Lewis Clark unfortunately has a Charcot neuropathy. He has some very significant problems where by bearing weight even with the best of offloading he still continued to form an ulcer he ended up having bone shaved down to take the pressure off, he healed but with his activity he developed a little bit more pressure and even with that bone being shaved down he formed another ulcer. In order not to regenerate bone infection, he decided to enroll in the study for Primatrix and he’s done extremely well.
So he had a wound?
Dr. Steven Kavros: He had a wound initially about a year ago
So he had it for 4 weeks or longer and then how quickly did he heal?
Dr. Steven Kavros: It was I believe about 6 weeks, from the Primatrix being applied until it healed.
And he hasn’t had any other since?
Dr. Steven Kavros: No, not since then.