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Diabetic Skin Ulcers Find Treatment With Hydrogels

Individuals who are diagnosed with diabetes have high blood sugar levels; this can impair blood circulation and accelerate nerve damage. When experiencing this, skin wounds struggle to heal by themselves, leading to what are called diabetic skin ulcers. Wounds like these take a long time to heal, increasing the risk of infection from external sources. What scientists from Washington University in St. Louis, Missouri has developed, however, may be another solution to a problem that may be impacting millions worldwide.

The technology they developed made use of what are known as hydrogels, which are 3D networks of hydrophilic polymers, or polymers with an affinity for water. This hydrophilicity allows their 3D structure to “swell” in the presence of water, carrying it within its structure. The scientists in this new study, published in the journal Science Advances, took advantage of this very property of hydrogels to allow it to carry and absorb certain substances, dispensing oxygen directly to the skin ulcers that need it for healing by applying the hydrogel directly over the wound in question.

The material in the study consists of two parts: oxygen-release microspheres (ORMs) and a reactive oxygen species (ROS)-scavenging hydrogel. The ORMs are made of tiny spheres—less than 5 µm (micrometers, 1×10-6 meters) in diameter—made of “bioeliminable” material conjugated with the enzyme catalase. Catalase, as an enzyme, facilitates the decomposition of hydrogen peroxide (H2O2), turning it into water (H2O) and oxygen (O2). The cores of these microspheres, on the other hand, contain a complex of a water-soluble polymer paired with H2O2.

The mechanism in which this novel material heals skin ulcers was developed to proceed as follows: once applied to the wound in question, the liquid transforms into a hydrogel through the patient’s body heat. Once this happens, the catalase locked in the ORMs’ shells react with the H2O2 inside their cores, releasing O2 gas into the hydrogel, which then aids the wound in healing as it is in direct contact with the diabetic skin ulcer. The oxygen-rich environment around the wound now assists it in healing over a two-week period, reducing swelling around the wound and promoting new skin growth.

Too much production of oxygen on the skin through this method, however, releases the unwanted ROS; too much ROS on the skin may cause skin cells to die, negating the healing process. The scientists devised a workaround for this through the hydrogel itself; the hydrogel absorbs the ROS that may be created through this process, capturing and destroying it in the process.

The scientists tested their new technology on diabetic mice, and performed tests with three groups: a group treated with the hydrogel with ORMs, a second group treated with the base hydrogel alone, and a third control group. By measuring the size of the ulcers on the mice before and after 16 days’ exposure with the new material, the study authors noted that ulcers on the mice treated with the full package were left with ulcers that were 10.7% of their original size after 16 days’ worth of treatment. By comparison, the second group (treated with hydrogels alone) had ulcer sizes reduced only by 30.4%, and the control group’s just by around half (52.2%) their ulcers’ original sizes. The authors noted that in measuring the thickness of the epidermis, or the outermost layer of the skin, on the three groups, they found out that the first group had the thickest layer measurement after eight days, while the same group had the thinnest measurement instead after the aforementioned 16 days. This, they say, showcases that the wounds were indeed healing, and that the ORM-infused hydrogels were truly lessening inflammation.

Lead author Jianjun Guan mentions that the study represents “a new therapeutic approach to accelerating healing of chronic diabetic wounds without drugs,” saying that it also “has the potential to treat other diseases in which oxygen is low, such as peripheral artery disease and coronary heart disease.” The team is planning to engage testing on larger animals, then following up with human clinical trials in the future.

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