Microalgae instead of a pressure chamber
Cyanobacteria patch heals chronic wounds in diabetes
Alice Bakhareva, N+1
Scientists from China has created a patch with cyanobacteria that saturate the wound with oxygen and promotes its healing. The patch was developed for chronic wounds that occur with diabetes. With the patch, the rate of wound healing in mice with diabetes was the same as in normal animals; the patch helped the skin graft to take root. The article was published in the journal Science Advances (Chen et al., Dissolved oxygen from microalgae-gel patch promotes chronic wound healing in diabetes).
Figures from the article by Chen et al.
A quarter of diabetic patients are at risk of developing chronic wounds, including diabetic foot – purulent-necrotic and ulcerative skin lesions, which in a neglected case lead to amputation. Constantly elevated blood glucose leads to hypoxia (lack of oxygen) in the tissues, as a result of which wounds cannot start the growth of blood vessels and the healing process.
They try to increase the flow of oxygen to the tissues of diabetic patients with the help of oxygen therapy: patients are placed in pressure chambers, where they breathe oxygen under high pressure, or gaseous oxygen is supplied locally to the wound area. However, these procedures increase the oxygen level only for one to two hours while the patient is in the chamber. As a result, treatment with gaseous oxygen is effective only in some cases; it is necessary to look for ways to deliver dissolved oxygen to wounds.
Scientists from Nanjing University under the leadership of Jinhui Wu (Jinhui Wu) decided to use Synechococcus elongatus cyanobacteria for local enrichment with dissolved oxygen. These unicellular creatures are capable of photosynthesis and produce oxygen from inorganic carbon compounds (carbon dioxide and carbonates). Cyanobacteria were placed in hydrogel balls with a diameter of one millimeter, from which plasters were made. The part of the patch adjacent to the skin was covered with a Teflon membrane with holes of 0.22 micrometers – through them the skin and the patch could exchange gases and liquids.
The structure of the patch with cyanobacteria.
In the light, the oxygen concentration in the patch with cyanobacteria increased from zero to 600 micromoles per liter. When additional sodium carbonate (a substrate for photosynthesis) was added to the hydrogel, the oxygen concentration doubled. Then the patch was tested on a piece of mouse skin. Dissolved oxygen penetrated through the skin more than a hundred times more effectively than with local oxygen therapy.
The concentration of oxygen in the solution under the skin. Red – if a patch is applied, black – with oxygen therapy.
The effect of the patch was studied in vitro and in vivo. To begin with, hypoxia was induced in the culture of skin fibroblasts, keratinocytes and endothelial cells – cells that play a key role in wound healing and vascular growth. To do this, the concentration of glucose in the medium was increased and oxygen access was limited. In vivo experiments, a patch was applied to wounds with a diameter of one centimeter, which were created in mice with artificially induced diabetes.
The patch reduced the content of the hypoxia marker in the tissue (p<0.001), increased fibroblast division (p<0.01), keratinocyte migration (p<0.01) and differentiation of endothelial cells (p<0.001).
Fibroblasts in culture after induction of hypoxia. On the top left – control, on the top right – during oxygen therapy. From below – with a patch with cyanobacteria in the dark or in the light.
In mice with diabetes, the wound did not heal even by day 15, whereas in control animals, scar healing took 12 days. The patch with cyanobacteria accelerated the process: the wound was healed by 45 percent in six days (with oxygen therapy at the same time, the skin was restored by only 20 percent) and completely buried after 12 days. Histological studies have also shown that the patch accelerates tissue repair and promotes vascular growth.
A: fresh wound; three, six and 12 days after surgery. From top to bottom: a mouse without diabetes, a control animal, with oxygen therapy, with a patch. B: the proportion of healed skin on the third, sixth and 12th day.
Finally, the researchers studied the effect of the patch on the skin graft. Large wounds are treated with skin grafts, but if vascular growth is impaired, the grafts do not take root. To test whether the patch helps to circumvent this restriction, mice were cut off a rectangular flap of skin with an area of two square centimeters. One of the sides of the flap was left connected to the skin of the mouse and watched how the raised area would take root back – this model simulates autotransplantation (tissue transplantation of the same individual).
In mice with diabetes, necrotic areas appeared on the skin flap on the second day after the operation, and on the fourth day the skin completely died off and disappeared. In control mice, areas of the flap also died off and disappeared on the sixth day. Oxygen therapy reduced the proportion of necrotized tissues to almost the control level (58 percent), and in animals with patches it was only 18 percent – the flap took root even better than in control animals (p<0.05).
A skin flap cut off and sewn back immediately after, two, four and six days after the operation. From top to bottom: a mouse without diabetes, a control animal, with oxygen therapy, with a patch.
There are also electronic patches for chronic wounds. They do not enrich the skin with oxygen, but release antibiotics when the temperature rises or the pH of the wound changes. Such a device does not promote self-healing of the wound, but helps to control its condition.
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