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Wound Care Q&A

Assessing The Roles And Timing Of Advanced Therapies For Wounds

The roles of advanced therapies within the wound care armamentarium and the timing of when to use them can be debatable. Accordingly, these expert panelists share their perspectives on modalities ranging from hyperbaric oxygen therapy to NPWT with instillation, and whether clinicians should reserve advanced therapies until a patient has had four weeks of non-healing.


Do you utilize hyperbaric oxygen therapy (HBOT)? When is it indicated and most beneficial?


Kazu Suzuki, DPM, CWS, uses HBOT very selectively. Although HBOT works based on literature and from his personal experience, Dr. Suzuki cautions his patients about the challenging logistics of getting to the HBOT clinic five days a week for four to six weeks to complete the treatment cycle. He warns patients that HBOT is certainly not a cure-all. However, Dr. Suzuki will utilize it for the diabetic foot with osteomyelitis, dehiscence (after a transmetatarsal amputation), skin graft or skin flap failure, based on the Undersea And Hyperbaric Medical Society guidelines.1

Alexander Reyzelman, DPM, rarely uses HBOT. If the patient has adequate arterial perfusion and one addresses infection effectively, Dr. Reyzelman says the wounds/ulcers do well. He also notes that the literature support for HBOT in healing diabetic foot ulcers is not definitive and is actually “quite controversial.” Dr. Reyzelman feels the use of HBOT for non-healing diabetic foot ulcers should be adjunctive.

Noting that the Medicare guidelines for HBOT are “very strict,” Dr. Reyzelman says Medicare will cover HBOT treatment for diabetic foot ulcers only if there is exposed bone.  

“I know that the camps for HBOT are drawn into evangelists and skeptics. I belong to neither,” says David G. Armstrong, DPM, MD, PhD.

While he believes HBOT can be helpful for some patients, Dr. Armstrong says there is a lack of data that clarifies who HBOT will help the most. He calls for companion diagnostics to help guide decisions for expensive, involved therapies such as HBOT.

When using HBOT, Dr. Suzuki also advises optimizing the patient’s blood flow to the legs. He relates treating a patient with diabetes with a severe leg wound who could not have revascularization due to her other medical issues. He treated the patient with HBOT anyway because limb preservation was at stake but she had minimal improvement after six weeks of HBOT treatment.

“The take-home message here is you need that blood flow. Otherwise, oxygen doesn’t get there to the target tissue,” says Dr. Suzuki.


Do you utilize cellular- and tissue-based products? How do you select which one to use?


Dr. Armstrong notes that for every one cultured tissue product he uses, he and his colleagues do 10 split-thickness skin grafts (STSGs). He emphasizes that cultured tissue products, by and large, are immune modulators. Dr. Armstrong says these products don’t behave like skin grafts because they are not. He uses amnion cultured tissue products to help facilitate partial take of the STSG. Dr. Armstrong prefers Integra (Integra LifeSciences) across joints and over exposed hardware/tendon in anticipation of the ultimate STSG.

Dr. Suzuki uses cellular- and tissue-based products, otherwise known as skin substitute grafts. He says one can use such products for just about any chronic wounds that do not heal after a four-week period in the outpatient setting. Dr. Suzuki also uses artificial skin graft in the acute care setting when an actual STSG is indicated but the patient refuses it, or if he or she does not have adequate skin to harvest. Dr. Suzuki says this is often an issue for patients of advanced age.

Dr. Reyzelman uses cellular- and tissue-based products, particularly those with good quality randomized controlled trials. He considers which products have good evidence and then looks at which of them have insurance coverage.

Which product to use is a tricky question, says Dr. Suzuki, as physicians must consider which products are available in one’s area versus the patient’s insurance coverage and one’s personal preference and experience as a wound care physician. As he notes, cellular- and tissue-based products can be very costly, especially if one is using them weekly until achieving wound closure.

Dr. Suzuki has tried and utilized most products on the market on his own patients. Generally, he says more expensive human tissue-based grafts such as EpiFix (MiMedx) or Grafix (Osiris Therapeutics) work exceedingly well. He notes animal-based grafts like PuraPly (Organogenesis) or Oasis (Smith and Nephew) are less expensive, thus allowing physicians to utilize them on a broader range of patients. Dr. Suzuki advises new clinicians to sample cellular and tissue-based products as much as they can and then stick with what they find the most compatible in their hands.

Dr. Suzuki adds that the latest amniotic tissue grafts (i.e. EpiFix) are so effective for chronic wounds that he uses less and less of the other advanced wound therapies these days.


Do you use medical maggots? When should you use them?


While Drs. Reyzelman and Suzuki have used medical maggots, they don’t do this often. As Dr. Reyzelman notes, one can use maggots on a wound that has slough, wounds that are too painful for surgical debridement and for patients who are not good candidates for surgical debridement. Similarly, Dr. Suzuki says maggots allow “very effective and usually painless debridement.” He would consider maggots for patients with very sensitive skin or who are extremely adverse to procedural pain from wound debridement.

Larvae can extend the time between debridements or reduce the need for debridement in very high-risk patients or in those in “wound hospice,” notes Dr. Armstrong. Often when physicians use larvae, he says the goal is not just to limit surgical intervention, it is just as important to increase “antibiotic-free days.”  

Dr. Suzuki cites treatment costs as an issue. He says the use of maggots is approximately $100 per application, which occurs every two days, possibly for one or two weeks, at a cost the patient pays.


When do you utilize negative pressure wound therapy (NPWT)? How about instillation NPWT?


Dr. Reyzelman often uses NPWT, saying one should use it on deeper wounds that need increased granulation tissue formation. He does not use NPWT on superficial ulcers/wounds. Once the ulcer/wound is at skin level and has 100 percent red granulation tissue base, Dr. Reyzelman advises discontinuing NPWT.

Likewise, Dr. Suzuki uses NPWT for deep, gaping wounds or filling in large tissue defects. He says there are “no other therapies on the market that do this better.” In addition, he says NPWT works so well that he and his colleagues are doing fewer and fewer plastic surgery consults for free muscle flaps (from back muscle to the foot, etc.). Dr. Suzuki also uses NPWT immediately after a skin graft (with a reduced pressure setting) to eliminate hematoma problems.

Instillation NPWT allows continuous or intermittent irrigation of a surgical wound, but Dr. Suzuki says this is usually utilized in acute care settings only. He cites data from Kim and colleagues that instillation NPWT reduces the length of hospital stay, which he says can save costs.2

“NPWT has done for tissue repair and wound healing what endovascular therapy has done for vascular surgery,” says Dr. Armstrong. “In other words, it has fundamentally transformed how people with complex tissue loss are treated.”

Whereas early in Dr. Armstrong’s career, 10 to 12 percent of people received some sort of free tissue transfer, he says that now happens less than 1 percent of the time in many clinics. Similarly, vascular surgery used to be entirely open in the 1990s whereas he says now eight in 10 vascular interventions are endovascular.  

Dr. Armstrong sees the pendulum swinging slightly back to increased use of free tissue transfers, particularly for very thin, low metabolic demand flaps like the superficial circumflex iliac perforator flap (SCIP). He describes this flap as similar to a vascularized full-thickness graft.


Do you really need to wait until there has been four weeks of non-healing prior to using advanced wound therapies?


As Dr. Suzuki notes, Sheehan and colleagues concluded that the percent change in diabetic foot ulcer area after four weeks of observation was a robust predictor of healing in 12 weeks.3 As he says, this timeframe enables clinicians to identify a problem wound that does not respond to the standard of care and swiftly incorporate advanced therapies. Although advanced therapies such as amniotic tissue grafts or HBOT can be highly effective in closing the wounds, Dr. Suzuki says physicians need to discuss the use and timing of such therapies beforehand with patients as advanced therapies can be burdensome to the patients.

Dr. Reyzelman points out that the reason for waiting to use advanced wound therapies is to comply with Medicare and other payor guidelines. However, if the ulcer/wound is not responding to standard of care (utilizing various topical treatment options), he says physicians should be able to use advanced therapy as necessary.

If the clinician can answer whether good quality offloading, assessment and improvement of vascular insufficiency and debridement are taking place, then Dr. Armstrong argues that the four-week non-healing guideline is really just a delay tactic. “We need to move from wound care to wound closure,” he says.

Dr. Armstrong is a Professor of Surgery at Keck School of Medicine at the University of Southern California. He is the Director of the Southwestern Academic Limb Salvage Alliance (SALSA).

Dr. Reyzelman is an Associate Professor at the California School of Podiatric Medicine at Samuel Merritt University. He is the Co-Director of the University of California San Francisco (UCSF) Center for Limb Preservation.

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


  1. Undersea & Hyperbaric Medical Society. Available at .
  2. Kim PJ, Attinger CE, Crist BD, et al. Negative pressure wound therapy with instillation: Review of evidence and recommendations. Wounds. 2015; 27(12):S2-S19.
  3. Sheehan P, Jones P, Caselli A, et al. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Diabetes Care. 2003;26(6):1879-82.

For a related article, see “Does NPWT With Instillation Have A Viable Role In The Wound Healing Process?” in the August 2018 issue of Podiatry Today. For other Wound Care Q&A columns, visit .

Wound Care Q&A
Clinical Editor: Kazu Suzuki, DPM, CWS
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