Continuing a discussion of bioengineered alternative tissues (BATs), these panelists discuss precautions to take before using BATs and when to avoid using them. They also offer their advice on approaching any new BATs that arrive on the market.
What are your clinical pearls or precautions before using BATs for your patients?
For Kazu Suzuki, DPM, CWS, the basics of best practice wound care apply to the proper use of BATs. He suggests ensuring proper blood flow and an absence of clinical infection before considering the use of BATs on lower extremity wounds.
Another concern is insurance coverage and Dr. Suzuki notes most BATs are expensive, ranging from $100 for a small piece to a few thousand of dollars for a large piece of cadaveric human skin allograft. Accordingly, he recommends getting pre-authorization before considering initiating BAT application rather than just assuming one will be reimbursed fully. For example, he recently treated the CEO of a large apparel company who had three private insurances. For that patient, Dr. Suzuki was able to get an approval for only a single application of BAT for his chronic diabetic foot ulcer.
What do you think is the best way to approach new BATs introduced to the market?
Although one might think the market for bioengineered alternative tissues is really saturated now with a few dozen different brands of BATs, Dr. Suzuki recently heard from an industry expert that there are close to 50 additional brands of BATs, mostly of human origin (amniotic membrane or cadaveric skin) submitted this year for review by the Centers for Medicare and Medicaid Services (CMS) for possible Medicare reimbursement. Dr. Suzuki cites a recent study that concluded that a bilayered living cell skin substitute was superior to an acellular collagen skin substitute, using data from a national wound-specific electronic medical record.1 With a wider adaptation of electronic medical records, he says we may see more of this interesting retrospective comparative data among various BATs.
Over the next several years, David G. Armstrong, DPM, MD, PhD, foresees the bar steadily elevating in regard to the requirement for good quality evidence to support many of these newer tissues. In the past, he says the profession has had only limited evidence for BAT products except for a few randomized controlled trials from between 10 and 15 years ago.
“However, the barrier to approval for these products has been so low that almost all companies have made strategic decisions not to support meaningful clinical development. That has changed significantly, however, and there are some that are investing heavily on the front end in investigating their product, which indicates to me that they are beginning to believe in data more than they might believe a four-color advertisement with a before and after photo,” says Dr. Armstrong.
When considering new bioengineered alternative tissues, Dr. Blume suggests evaluating the underlying research model and scientific basis for the product. He says when considering a new bioengineered alternative tissue, the BAT should have clinical evaluation in the current patient population with full disclosure.
With any new product, Dr. Suzuki would ask the company representative to show him all the literature they have at that point. He says some of the companies have an impressive array of scientific literature behind the BAT while other modalities may be considered “me too” products that are just similar to the existing BAT product and sourced from the same human tissue bank. Dr. Suzuki has found that most companies do offer a free trial of the product for one or a few wound patients for several weeks or until wound closure. He notes one would have to sign a waiver that one will not bill for these “free” BAT grafts.
“I think it is a nice way to find out if you like the handling of the product and how it performs on your own patient population,” says Dr. Suzuki of the samples.
In which scenarios would you avoid using BATs?
Dr. Blume would not use a bioengineered alternative tissue in any wound that may have bioburden, infection or a lack of perfusion.
Likewise, Dr. Suzuki advises against using BATs in patients with infections. If one is dealing with chronic wounds that are not responding to treatments for a few weeks and if there is any suspicion that there may be low-grade or subclinical wound infection, he suggests taking a good wound culture (after debriding sharply and irrigating the wound base with normal saline) and treating the wound empirically. His antibiotic of choice in the outpatient wound clinic is doxycycline (Vibramycin, Pfizer) 100 mg twice a day for seven to 10 days, an agent that covers Staphylococcus aureus, including most methicillin resistant S. aureus (MRSA). Dr. Suzuki says patients appear to tolerate doxycycline better than trimethoprim/sulfamethoxazole (Bactrim, Roche), which also has a myriad of drug interactions, including interactions with warfarin (Coumadin, Bristol-Myers Squibb) and many others. Doxycycline also has an anti-inflammatory effect, which he notes may be helpful with wound healing and pain control as well.
Dr. Suzuki also cautions against using BATs in possibly malignant wounds. If a chronic wound is present for more than six months and is not responding to local wound care treatment, he generally recommends performing a wound biopsy to make sure there is no skin cancer within the wound. He sees many patients with squamous cell and basal cell carcinoma in legs and feet, especially in fair-skinned patients and patients 80 years of age and older. If older patients are from California or Florida, Dr. Suzuki thinks of that as a red flag for skin cancer as they are part of the generation that routinely sunbathed without sunscreen use.
Dr. Armstrong is a Professor of Surgery and Director of the Southern Arizona Limb Salvage Alliance (SALSA) at the University of Arizona College of Medicine.
Dr. Blume is an Assistant Clinical Professor of Surgery in the Department of Surgery and an Assistant Clinical Professor of Orthopaedics and Rehabilitation in the Department of Orthopaedics, Section of Podiatric Surgery at the Yale University School of Medicine in New Haven, Ct. Dr. Blume is a Fellow of the American College of Foot and Ankle Surgeons.
Dr. Suzuki is the Medical Director of the Tower Wound Care Center 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. Dr. Suzuki can be reached via e-mail at Kazu.Suzuki@CSHS.org .
1. Marston WA, Sabolinski ML, Parsons NB, Kirsner RS. Comparative effectiveness of bilayered living cellular construct and a porcine collagen wound dressing in the treatment of venous leg ulcers. Wound Repair Regen. 2014; 22(3):334-40.