With increasing numbers of cellular and tissue-based products emerging on the market, these panelists discuss when to use such products, and which products are most effective.
When do you decide a patient needs a cellular- or tissuebased product?
John Steinberg, DPM, FACFAS, emphasizes that the first task with wounds is proper determination of the wound etiology. He says clinicians should not apply any cellular- or tissue-based products until they have addressed the cause of the wound (i.e., equinus, prominent bone, infection, ischemia). After addressing this primary etiology, Dr. Steinberg says one can then augment any delayed wound healing with a cellular- or tissue-based product.
Jeffrey Lehrman, DPM, FASPS, considers cellular- or tissue-based products for any chronic ulcer that isn’t responding and healing as quickly as it should. As Dr. Lehrman notes, most define chronicity of a venous leg ulcer as not being 40 percent smaller after four weeks of treatment and a chronic diabetic foot ulcer as not being 50 percent smaller after four weeks of treatment, guidelines he will usually use when employing these products.1 Likewise, Christopher Winters, DPM, will consider using cellular- or tissue-based products if the wound has not decreased 50 percent in size in four weeks with conservative care.
Despite the four-week non-healing benchmark for wounds, Kazu Suzuki, DPM, CWS, notes that in reality, most wound patients in his wound care center have had their wounds for well over two to three months by the time they get referrals to him so most of his patients would qualify for the need for a tissue-based skin substitute graft.
“To put it another way, since there is a robust body of medical evidence that the use of tissue-based skin substitute grafts closes the wound much faster over the ‘standard of care’ including proper wound debridement and sterile moist dressing, I don’t see a good reason to ‘hold back’ or ‘refrain’ from using these products that close the wound much faster versus the conventional therapy,” says Dr. Suzuki.
Paul Kim, DPM, FACFAS, notes that in the clinic, one should reserve the use of cellular- or tissue-based products for patients whose wounds are not progressing with fundamental approaches (offloading, compression, debridement, etc.). He says one should ensure optimal perfusion and address venous ablation and bacterial control prior to considering any of these products. Although Dr. Kim prefers surgical treatment (e.g. biomechanical surgery) over more conservative clinic-based options to treat wounds, he says sometimes OR access or patient preference prohibit this approach. For these cases, Dr. Kim says cellular- or tissue-based products may provide viable options.
“I do not believe the use of any of these cellular- or tissue-based products as front-line therapy or weekly application of any of these products without demonstrable improvement is a sensible approach,” maintains Dr. Kim.
In the operating room, Dr. Kim says the gold standard remains a split-thickness skin graft (STSG) or local/free tissue flaps. However, he notes there are occasions when using these modalities is not possible or appropriate. For example, Dr. Kim says if there are exposed deep structures, one can cover these until a neodermis forms. Thus, he notes a scaffold product may be necessary prior to a staged STSG application.
If a provider’s Medicare Administrative Contractor (MAC) has a skin substitute Local Care Determination (LCD), and Dr. Lehrman says most do, he says this standard may guide the use of cellular- or tissue-based products.
For which wounds do you most often prescribe cellular- or tissue-based products?
When it comes to cellular- or tissue-based products, Dr. Steinberg will apply them for clean, non-ischemic wounds that have not healed after four weeks of debridement, offloading and local wound care. As he says, such wounds will often be in a state of cellular senescence and the grafted biology delivered from the cellular- or tissue-based product may serve to reinitiate the healing pathway.
Dr. Suzuki does not differentiate the wound etiology when using cellular- or tissue-based products unless there is a clear FDA indication for using a specific product. For example, he says Dermagraft (Organogenesis) is indicated only for diabetic foot ulcers. In Dr. Suzuki’s experience, all the cellular-based products work just the same on healing wounds (regardless of the wound etiology) as long as the clinician has ensured adequate wound bed preparation and perfusion. In other words, the wound must be free of necrotic and non-viable tissues, and free of infection with the patient having enough blood flow to the wound base and having adequate nutritional intake, according to Dr. Suzuki.
Dr. Lehrman most often uses cellular- or tissue-based products on diabetic foot ulcers. As he notes, there are different indications with some cellular- or tissue-based products indicated for diabetic foot ulcers only, others for diabetic foot or venous leg ulcers only, and others for use on any chronic ulcer from head to toe.
“I think the fact that I use cellular- or tissue-based products on diabetic foot ulcers most often is a reflection of my patient population, and that diabetic foot ulcers very often fall into the category of being considered chronic,” acknowledges Dr. Lehrman.
Dr. Winters most often prescribes cellular- or tissue-based products on diabetic foot and venous leg ulcers, but has also used the modalities on dehisced surgical wounds and pressure ulcers.
More important than classifying the wound type, notes Dr. Kim, is addressing the underlying cause rather than fixating on which product to choose.
Which cellular- or tissue-based products have you found effective?
In his experience, Dr. Winters has found the most effective cellular- or tissue-based products to be Apligraf (Organogenesis), TheraSkin (Soluble Systems), Omega3 (Kerecis), PriMatrix (Integra LifeSciences) and Stravix (Osiris Therapeutics).
Dr. Suzuki notes has used various cellular- or tissue-based products on the market, and finds them all very effective in closing the chronic wounds that were previously considered to be challenging to close with conventional therapies.
“In general, I do believe ‘you get what you pay for’ may apply,” says Dr. Suzuki.
Anecdotally, Dr. Suzuki notes that more expensive grafts (such as human tissue-based amniotic membrane grafts) tend to work better and possibly faster in wound closure than less expensive grafts (such as animal-based collagen grafts). In reality, he notes the reimbursement scheme for skin substitute grafts is complex and he has his own method to pick and choose the most appropriate product based on the patient’s own insurance coverage and co-pay limitations.
Dr. Suzuki notes a few studies have compared tissue-based skin substitute grafts but all of the studies were retrospective and the results have been conflicting with one study claiming superiority of one modality over the other, and vice versa.2 Dr. Suzuki feels the best study design would be a “head-to-head” prospective randomized controlled trial comparing one product to the other but he says it may never be conducted as it would be very expensive to do.
“Frankly, I don’t see much point in conducting such a study as all of these tissue-based skin substitute grafts are equally efficacious in closing the wounds over the conventional wound care methods (debridement and moist wound dressing),” notes Dr. Suzuki.
Dr. Steinberg notes there is very little comparative data between the cellular- or tissue-based products, and many of them have similar components. He cites good clinical outcomes and experience with Integra (Integra LifeSciences) and Grafix (Osiris Therapeutics) in his patient population, but says each provider should evaluate the products that best serve the patient’s needs.
Dr. Suzuki says the challenge may be to convince enough wound care clinicians to buy into the idea of using tissue-based grafts. He says another issue is the proper selection and timing of using these advanced modalities, knowing when to mix and match these tissue-based skin substitute grafts with hyperbaric oxygen therapy (HBOT) in comparison to negative pressure wound therapy (NPWT).
Dr. Kim emphasizes that clinicians should be judicious in their use of cellular- or tissue-based therapies “ … due to their added burden on healthcare resources.” He notes seeking high-level evidence from robust studies by reputable investigators is a good starting point in selecting the most appropriate product.
“We have to be smart consumers and attempt to make independent decisions on what is the best for our patients,” says Dr. Kim.
Dr. Kim is an Associate Professor at the Georgetown University School of Medicine. He is the Vice Chair of Research at MedStar Plastic and Reconstructive Surgery. Dr. Kim is a Fellow of the American College of Foot and Ankle Surgeons.
Dr. Lehrman is on the American Podiatric Medical Association (APMA) Coding Committee, serves as an expert panelist on Codingline.com and is a Fellow of the American Academy of Podiatric Practice Management (AAPPM). Follow him on Twitter @DrLehrman .
Dr. Steinberg is a Professor in the Department of Plastic Surgery at the MedStar Washington Hospital Center in Washington, DC. He is a Fellow and President-Elect of the American College of Foot and Ankle Surgeons.
Dr. Suzuki is the Medical Director of the Tower Wound Care Centers at the Cedars-Sinai Medical Towers. He is also on the medical staff of the Cedars-Sinai Medical Center in Los Angeles and is a Visiting Professor at the Tokyo Medical and Dental University in Tokyo. He can be reached at Kazu.Suzuki@cshs.org.
Dr. Winters is affiliated with the American Health Network in the Indianapolis area and many hospitals in Indiana. He is board-certified in wound care by the Council for Medical Education and Testing, and is board-certified in the prevention and treatment of diabetic foot wounds and footwear by the American Board of Multiple Specialties in Podiatry.
1. Sheehan P, Jones P, Caselli A, et al. Percent change in wound healing of diabetic foot ulcers over a four-week period is a robust predictor of complete healing in a 12-week prospective trial. Diabetes Care. 2003; 26(6):1879-82.
2. Suzuki K, Michael G, Tamire Y. Viable intact cryo-preserved human placental membrane for a non-surgical approach to closure in complex wounds. J Wound Care. 2016; 25(Suppl 10):S25–31.