By Temple University School of Podiatric Medicine Journal Review Club
Article Title: Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer
Authors: Cao Y, Gang X, Wang G
Journal: J Diabetes Res....
By Windy Cole, DPM
In my recent WoundSource webinar, I discussed the topic of diabetic foot ulcers (DFUs) and using advanced therapies to encourage their healing. The webinar is still available for viewing on WoundSource.com. Chronic lower extremity wounds present significant challenges with regard to effective wound management. Ischemia, microcirculatory dysfunction and peripheral vascular disease cause limitations in blood flow that can delay the healing process.
In the webinar, I addressed:
- Old and new perfusion assessment methods
- Case studies of difficult to heal DFUs
- Detailed data on different interventions to encourage healing in DFUs
Below are answers to some of the frequently asked questions that were submitted during the webinar.
Frequently Asked Questions
Question: Can nurses grade diabetic lower extremity wounds by using the Wagner grading criteria?
Answer: Any clinician treating diabetic foot ulcers (DFUs) can utilize the Wagner ulcer classification system. The Wagner system assesses ulcer depth and the presence of osteomyelitis or gangrene by using the following grades: grade 0 (pre-or post-ulcerative lesion), grade 1 (partial- or full-thickness ulcer), grade 2 (probing to tendon or capsule), grade 3 (deep with osteitis), grade 4 (partial foot gangrene), and grade 5 (whole foot gangrene).
Question: What are your thoughts on or experience with topical oxygen treatment for DFUs?
Answer: It has been my experience that continuous topical oxygen therapy (cTOT) offers an effective non-invasive chronic wound treatment that may speed healing in DFUs by improving microcirculation and oxygenated hemoglobin.
Question: What are your thoughts on utilizing hyperbaric oxygen therapy (HBOT) to treat DFUs?
Answer: HBOT delivers high-pressure 100% oxygen to the tissue in the hopes of increasing wound oxygenation. HBOT relies on adequate arterial perfusion to transfer oxygen to the wounded tissue. Most commonly, DFUs need to be Wagner grade 3 or higher to potentially qualify for HBOT, and prior authorization is necessary. It has been my experience that successful wound healing occurs as a culmination of multiple evidence-based therapeutic modalities working in conjunction.
Question: In DFUs, there is usually an excess of matrix metalloproteinases (MMPs) and a decrease of tissue inhibitors of metalloproteinases (TIMPs). Do you know of any treatments to balance them?
Answer: Indeed, excess protease activity can lead to chronic non-healing wounds. Recent research has led to development of many new MMP modulators, including protease-absorbing dressings, micro-RNA regulation therapies, and utilization of signaling molecules and peptides. Knowing the mechanism of action of your chosen wound care therapy will allow for proper product selection.
Question: Is pulsed acoustic cellular expression (PACE) therapy similar to ultrasound? I have used laser therapy and e-stim for some diabetic ulcer with good outcomes as well.
Answer: PACE therapy is based on extracorporeal shock wave technology (ESWT) used for over 30 years in lithotripsy. The device works by creating and collapsing a vapor bubble caused by a high-voltage spark in a fluid medium. The energy generated by the acoustic wave is then focused to a target tissue site. The biological effect that is produced promotes neovascularization and leads to improved healing in chronic, recalcitrant diabetic ulcerations.
Question: Does high blood glucose interfere with grafts? Can it "kill" the graft?
Answer: Overall, compared with non-diabetic patients, diabetic patients experienced a significantly higher risk of delayed healing time and complications, including infection. Optimizing glycemic control is key to maximizing wound healing no matter what product is used. Individual Medicare Local Coverage Determinations stipulate a maximum hemoglobin A1c that a patient can have before utilizing any cellular and/or tissue product. I recommend consulting this document.
Question: Do you see frequent patient tissue reactivity to cellular and/or tissue-based products (CTPs) in your practice?
Answer: CTPs have emerged as comprising one of the most promising groups of advanced wound care therapies for the management of DFUs. As a whole, this category of advanced therapies supports cellular functions essential for wound healing. The ideal CTP is non-toxic, has no antigenicity, is immunologically compatible, and does not transmit disease. I have not had a problem with reactivity in my patients, but I typically steer clear of xenografts to avoid inflammatory responses.
Question: If patients have problems with compliance with devices, when is a mental health consultation appropriate to help address resistance to lifestyle change?
Answer: I believe that at least some attempt should be made to explore the reasons for non-compliance. Having frequent discussions with patients about their disease and other problems has proven to be beneficial. I never hold back on praise, either, because when patients have good blood glucose results, some encouraging words will make them proud and confident. Patients know that whenever they wish to call the clinic for help or information, they are free to do so at any time. Establishing a therapeutic alliance is key.
Question: Do you ever use negative pressure wound therapy (NPWT) in DFU treatment?
Answer: Wound healing can be impaired by both systemic factors, such as diabetes, and local factors, including excessive exudate, poor granulation tissue formation, and the presence of microorganisms, slough, and non-viable tissue in the wound bed. NPWT has been essential in providing favorable clinical outcomes in my DFU patient population.
Question: When choosing a CTP, what evidence or criteria do you look for?
Answer: This is a complex question without a straightforward answer. I typically weigh several factors to choose the right CTP for each wound. Here are a few things to consider:
- Wound type and characteristics. Is the wound full-thickness, are there exposed structures, is there devitalized tissue present?
- What level of evidence is found in the literature regarding efficacy of the product in the treatment of DFUs? Is there high-certainty data from randomized controlled trials or only low-level evidence based on observational case studies?
- What products are on my hospital or clinic formulary?
- What is insurance coverage like for each specific patient?
- What is the ease of use? Packaging, storage, shelf-life?
- Always take into account a patient's religious or personal beliefs and/or allergies
About the Author
Dr. Windy Cole holds a bachelor's degree in biology from the University of Cincinnati and is a graduate of the Kent State University College of Podiatric Medicine. Dr. Cole practices in Northeast Ohio where she serves as Medical Director of the Wound Care Center, University Hospitals Ahuja Medical Center and as Adjunct Professor and Director of Wound Care Research at Kent State University College of Podiatric Medicine. A dedicated wound care advocate for two decades, Dr. Cole is interested in medical education, diabetic foot care, wound care, limb salvage, and clinical research. Her passion to help others has led her to humanitarian efforts, including a medical mission to Jordan in 2018 to aid Syrian refugees. Dr. Cole has published numerous articles and is in demand as a speaker both nationally and internationally. She is a feature writer for Podiatry Management and Today's Wound Clinic and is a contributing writer for Podiatry Today.
The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, Kestrel Health Information, Inc., its affiliates, or subsidiary companies.