Capillaries are channels for the passage of blood and its contents (Figure1). Hydrostatic pressure and blood flow in the capillaries are greatly reduced. So that oxygen, nutrients and also the products of cell metabolism can be exchanged in sufficient time. Therefore, capillary density should be proportional to cellular mass. As the number of cells increases (hyperplasia), capillary to cell ratio decreases, resulting in cellular hypoxia. With tissue hypoxia, platelets become activated and begin to secrete Vascular Endothelial Growth Factor (VEGF). Under natural conditions, these factors affect the formation of capillaries in proportion to existing hyperplasia by acting on fibroblasts.
Capillary destruction (microangiopathy) is a major complication of long-term diabetes (Figure2). Therefore, administration of fibroblasts or Platelet-Rich Plasma (PRP) to the wound site at first sight may assume to improve capillary density resuting in increse blood flow and provide wound healing. however, In diabetic wounds the cause of the capillary-to-cell ratio disorder is not cell proliferation (hyperplasia) but is capillary destruction due to fluctuations in blood sugar. Fluctuations in blood sugar impose hypoxia on peripheral tissues, leading to failure of capillary-genesis process by platelets and fibroblasts. Under such condition, the body's natural mechanisms work to regenerate capillaries, but their activity will not be effective due to hypoxia. By removing the existing tissue hypoxia by hyperbaric oxygen therapy, the body's natural mechanisms get effective and capillary formation (angiogenesis) occurs, which finally improves blood flow. Improving blood flow is necessary for wound healing. Therefore, PRP or fibroblasts can only be effective in diabetic foot ulcers in the presence of sufficient blood flow and tissue oxygenation. Hyperbaric oxygen therapy increases the tissue oxygenation (directly, Figure3) and blood flow (indirect oxygenation, Figure4), enabling the success of fibroblasts and PRP in the treatment of diabetic foot ulcers.
