A blister on the heel. A minor cut that snags on a sock. For the majority of us, these are trivial, disappearing in a week and quickly forgotten. For an individual with diabetes, however, the same slight breach in the skin can remain open for months, resist closure, become infected, and potentially lead to amputation. The harrowing statistics are well established: approximately four out of ten of these foot ulcers recur within a year, and the five-year mortality rate for those with diabetic foot issues surpasses that of most cancers, only outdone by lung cancer. The wounds themselves are not unusual. What renders them fatal is the simple lack of blood flow.
This is the gap that a group spanning the University of New Mexico, Texas A&M, and a small Oregon firm named Exhalix seeks to bridge, and their solution is somewhat unconventional. They aim to treat these wounds with a toxin.
Hydrogen sulfide is the gas that imparts the odor of rotten eggs, and in any significant quantity, it is harmful. Yet, the body produces minuscule amounts of it intentionally, and at these negligible concentrations, it proves to be a remarkably sophisticated signaling molecule. It relaxes blood vessels, causing them to expand (vasodilation, if you prefer the technical term), and encourages the tissue to generate new vessels. More vessels, wider vessels, increased blood flow. In diabetes, the body’s natural production of this gas declines, which is a contributing factor to the poor circulation in an injured foot initially.
Thus, the reasoning follows naturally: reintroduce the gas. The challenge has always been the method. Deliver hydrogen sulfide throughout the entire body and you create precisely the situation you sought to prevent, but everywhere simultaneously.
The risk is the very essence of the approach.
“If that effect were to occur all over the body, your blood pressure would fall excessively because all your vessels would open simultaneously,” explains Dr. Cristine Heaps, interim head of the Department of Physiology and Pharmacology at Texas A&M’s College of Veterinary Medicine and Biomedical Sciences. “By maintaining a localized application, we can focus on the wound without impacting the rest of the body.” Opening the vessels everywhere causes blood to rush away from the organs that require it, including the brain. Systemic delivery also introduces a host of more severe risks, including cytotoxicity and liver damage. The gas that aids the foot could potentially lead to heart failure.
The device the team has developed, known as H2EALS, sidesteps this issue by not containing any gas. Instead, it features a layer of silver sulfide, a stable, shelf-stable solid that remains inactive until activated. When a small electric current passes through it (less than one volt, akin to what a coin battery provides), the coating releases its sulfur, and hydrogen sulfide is generated right there within the dressing, as needed, molecule by molecule. The cartridge operates on a 2032 battery, the same flat disc used to power a car key fob, and it is activated by tapping a phone against it. A clinician could, theoretically, program a slow release of five nanomoles per hour or a single measured dose once daily, for two weeks.
That control is the crucial aspect, and the lab results support it: across repeated tests, the delivered dose aligned with the target at a correlation of 0.998, an agreement that satisfies engineers. The gas is delicate, though. In the warm, moist, oxygen-rich environment of a dressing, it oxidizes and diminishes within minutes, and the absorbent padding of the wound consumes some of the dose, especially when damp. None of this is disastrous for the concept, but it necessitates careful metering rather than a simple switch-on.
Remaining in place
The true evaluation was whether the gas would remain where it was applied. In rats, doses ranging from 25 to 100 nanomoles were rapidly absorbed by the wound bed, and blood flow increased in correspondence with the dosage, with higher amounts causing a noticeable rise in perfusion. Both male and female rats displayed similar responses. The team then advanced to pigs, whose skin closely resembles ours, and purposefully created deprived, low-circulation wounds to simulate the human condition. Here, they administered doses up to 500 nanomoles, searching for the gas in locations it should not be: in the animals’ breath and patches of skin away from the wound. They found nothing. No detectable increase, even at the highest dose. The toxin, it appears, knows how to remain localized.
There is also an intriguing second phase to this research. One of the common methods for challenging wounds is negative pressure therapy, the regulated suction that extracts fluid and promotes tissue healing. The team is now attempting to combine the two, allowing the gas to perform its function for a