A Guide To Emerging Advances In Diabetic Foot Ulcer Healing
Over the past decade, the podiatric profession has seen an array of advances in diabetic foot ulcer healing. These advances ranged from the advent of a platelet-derived growth factor (Regranex, Johnson and Johnson) and negative pressure wound therapy (VAC therapy, KCI) to hydroscalpel debridement (Versajet, Smith and Nephew) and various prediction models (University of Texas Diabetic Foot Ulcer and Foot Risk Classifications).
Fortunately, there are even more modalities on the horizon that I believe will make an impact in the manner we treat these difficult problems. For the purpose of classification, I have divided these modalities into three simple categories: vascular, infection and pressure. Lawrence Harkless, DPM, taught me and many others that the first issues to address with any new diabetic foot wound are the “VIPs.” It is an easy acronym to remember for vascular, infection and pressure, and represents the wound’s macroenvironment. Most diabetic foot ulcers will heal in a timely fashion when we mitigate these three areas.
Key Diagnostic Tools For Assessing Microvascular Disease
While clinicians use the ankle-brachial index, segmental pressures and angiography to help diagnose macrovascular peripheral arterial disease (PAD), two new tools have emerged to aid in the diagnosis of microvascular disease. They are the SensiLase System (Vasamed) and the OxyVu® (HyperMed).
SensiLase measures skin perfusion pressure (SPP), which is the blood pressure at the capillary level in the skin. Normal SPP is greater than 50 mmHg. SPP measurement from 30 to 50 mmHg is diagnostic for PAD or microvascular disease and a reading of less than 30 mmHg denotes severe vasculopathy. Obtaining SPP can help predict diabetic wound healing. If SPP is greater than 40 mmHg, there is a high probability for wound healing. If it is 30 mmHg, there is only an 85 percent chance of healing. If it is 25 mmHg, the probability of healing drops to nearly 50 percent.1
The OxyVu uses hyperspectral imaging that was developed by the military to detect targets underneath forest canopies from sensors on aircraft above. The OxyVu is a camera that detects the wavelength of light emitted by oxyhemoglobin and deoxyhemoglobin in the skin. The computer interprets the readings and gives the values of these two molecules superimposed on a colorful photo of the foot. One study, which validated this device’s ability to predict healing in the foot wounds of patients with type 1 diabetes, found that an oxyhemoglobin level greater than 45 was a sensitive predictor of wound healing.2
What About Gene Therapy And Stem Cell Transplants?
In regard to the treatment of PAD, gene transfer therapy and stem cell transplantation are undergoing human trials. These may provide treatment options for patients who are not candidates for surgical revascularization or endovascular procedures.
Gene transfer therapy is promising as it may induce angiogenesis and inhibit restenosis, thereby restoring blood flow to ischemic tissue.3 One clinical trial is evaluating gene transfer via the injection of a plasmid DNA containing hepatocyte growth factor into the limbs of patients with non-reconstructable critical limb ischemia (CLI).4 Hepatocyte growth factor is an angiogenic growth factor secreted by vascular endothelial cells.5 Similarly, vascular endothelial growth factor (VEGF) is promising as a transfer gene for CLI.6
A recent search on www.clinicaltrials.gov revealed three trials that are actively recruiting patients with CLI or intermittent claudication for gene transfer therapy.
Researchers have shown that marrow-derived stem cells are effective in restoring contractility and perfusion after acute myocardial infarction.7 A randomized controlled study has assessed the injection of bone marrow mononuclear cells into the gastrocnemius muscle of ischemic limbs.8 The authors found improvements in transcutaneous oxygen measurements, pain-free walking times and rest pain in the treatment group.