Dr. Frykberg is podiatry chief and residency director and Dr. Banks is a research fellow, both at the Phoenix VA Health Care System in Arizona. Dr. Frykberg is a professor of practice at the University of Arizona College of Medicine in Phoenix. Dr. Banks is a professor at Grand Canyon University in Phoenix.
Author disclosures Dr. Frykberg has received research support from Osiris Therapeutics, Advanced BioHealing, AOTI, KCI, Smith & Nephew, Tissue Regenix, and ACell. All other authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Potential disadvantages of the TCC include the need for expertise in its proper application, the need for weekly cast changes, and related costs.24,35 Although a number of new devices have been introduced as alternatives to the TCC, only several clinical studies demonstrating their efficacy have been published.5,14,25,36 If nonweight bearing with crutches, wheelchair, or more effective devices are not feasible, even a pressure-attenuating insert can be used in a simple postoperative shoe until specialty referral is made.
Debridement of necrotic, callus, fibrous, and senescent tissues is a mainstay of ulcer therapy.42,43 It is considered the first and the most important therapeutic step leading to wound closure in patients with DFU.42-44 Unhealthy tissue must be sharply debrided back to bleeding tissue to fully visualize the extent of the ulcer as well as to detect any underlying abscesses or sinuses. It has been reported that regular (weekly) sharp debridement is associated with more rapid healing of ulcers compared with less frequent debridement.45-47 Wilcox and colleagues indicated that frequent debridement healed more wounds in a shorter time (P < .001).46 The more frequent the debridement, the better the healing outcome. There are different types of debridement methods, including surgical, enzymatic, autolytic, mechanical, and biologic.48 Surgical or sharp debridement can convert a chronic ulcer into an acute wound that is more likely to heal.24 Adequate debridement must always precede the application of topical wound healing agents, dressings, or wound closure procedures.24 Conversely, a wound that does not receive the necessary debridement is one that has not been adequately treated.
There are numerous types of dressings that have been developed over the past decade that promote wound healing. Few have undergone any formal clinical studies to determine efficacy or effectiveness to help guide clinicians in their use.
Yazdanpanah and colleagues argued that dressings should confer moisture balance, protease sequestration, growth factor stimulation, antimicrobial activity, oxygen permeability, and the capacity to promote autolytic debridement to facilitate the production of granulation tissues and the re-epithelialization process.24 In addition, it should have a prolonged time of action, high efficiency, and protection against contamination or infection.17 The group noted that no single dressing fulfills all the requirements of a diabetic patient with a foot ulcer. The choice of dressing is largely determined by the causes of DFU, wound location, depth, amount of scar or slough, exudates, condition of wound margins, presence of infection and pain, need for adhesiveness, and conformability of the dressing (Table 2).
Advanced Therapies
In 2003, Sheehan and colleagues reported that a 50% change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks.49 In addition, wounds failing to achieve a 50% reduction in area after 4 weeks need to be reassessed and considered for advanced treatment modalities if there are no otherwise identified impediments to wound healing.6,9,38 These findings have served as a pivotal clinical decision point in the care of DFUs over the past several years for early identification of patients who may not respond to the standard of care. Today, most wound care protocols advocate use of standard therapies for at least 4 weeks before advanced therapies are considered.
Significant improvements have been achieved in the treatment of ulcerations, and today clinicians have several advanced therapeutic options for management of chronic DFUs. These new technologies have been shown to increase the probability of complete wound closure in difficult-to-heal foot ulcerations in patients with diabetes. Among these are recombinant platelet-derived growth factors, a human living skin equivalent, and a human fibroblast-derived dermal substitute.49-51 Tissue-engineered skin equivalent (Apligraf) and human dermis (Dermagraft) are types of biologically active dressings that are derived from fibroblasts of neonatal foreskins.
The most recent advancements for wound care therapies is that of stem cell therapies, primarily bone marrow-derived and, most recently, placental-derived stem cells, including dehydrated human amnion chorion (Epifix) and amniotic matrix with mesenchymal stem cells (Grafix).52,53 Because of the expense of these products, they cannot be used universally in the treatment of DFUs but rather are used and reserved for difficult-to-heal wounds. In addition, negative pressure therapy has assumed a major role in the management of traumatic, acute, and chronic wounds and has shown efficacy in healing DFUs.54-57 Hyperbaric oxygen therapy and several biophysical modalities have been studied and found to be efficacious in healing a wide variety of chronic wounds over the past decade as well, although results vary by study, and no advanced modality has become universal in its application.58-64
