Hyperbaric oxygen therapy for wound healing in diabetic rats: Varying efficacy after a clinically-based protocol.

Hyperbaric oxygen therapy (HBOT) is a clinical treatment in which a patient breathes pure oxygen for a limited period of time at an increased pressure. Although this therapy has been used for decades to assist wound healing, its efficacy for many conditions is unproven and its mechanism of action is not yet fully clarified. This study investigated the effects of HBOT on wound healing using a diabetes-impaired pressure ulcer rat model. Seven weeks after streptozotocin-induced diabetes in rats (n = 55), a pressure ulcer was created on dorsal skin. Subsequently, animals received HBOT during 6 weeks following a standard clinical protocol (HBOT group with varying endpoints up to 42 days post-wounding) versus controls without HBOT. Capillary venous oxygen saturation (SO2) showed a significant increase in the HBOT group on day 24; however, this increase was significant at this time point only. The quantity of hemoglobin in the micro-blood vessels (rHB) showed a significant decrease in the HBOT group on days 21 and 42, and showed a trend to decrease on day 31. Blood flow in the microcirculation showed a significant increase on days 17, 21 and 31 but a significant decrease on days 24 and 28. Inflammation scoring showed significantly decreased CD68 counts in the HBOT group on day 42, but not in the early stages of wound healing. Animals in the HBOT group showed a trend for an increase in mean wound breaking strength on day 42.

Fibrin improves skin wound perfusion in a diabetic rat model.

The fibrin matrix of the thrombus that is formed directly after wounding, is an important determinant of the success of the early phase of wound healing. This phase is often impaired in patients with diabetes. A promising approach to improve skin wound healing is the application of a pro-angiogenic fibrin matrix onto the wound. We studied this in 59 female WAG/RijCrl diabetic rats, in which we created two dorsal full-thickness wounds of which one was treated with a human physiological fibrin matrix (2mg/ml) and one with PBS as control. Wound healing parameters were determined at different time points. The wound closure was significantly improved in fibrin-treated wounds on day 3 and 7. Also, fibrin-treated wounds showed a significantly higher perfusion on day 28 and 35 compared to control wounds (p<0.05). CD68 staining revealed that human fibrin did not induce an immune response. IN CONCLUSION: the application of a fibrin matrix on a diabetic wound showed improved perfusion and an increased early closure rate of the wound area.

Hyperbaric oxygen therapy to treat diabetes impaired wound healing in rats.

Wound healing in diabetes is frequently impaired and its treatment remains a challenge. Hyperbaric oxygen therapy (HBOT) receives a wide attendance and is often used as a last resort treatment option, however, its effectiveness for many conditions is unproven. We tested the effect of HBOT on healing of diabetic ulcers in an animal experimental setting. Experimental diabetes was induced by intraperitoneal injection of streptozotocin. Four weeks after diabetes induction, rats were ulcerated by clamping a pair of magnet disks on the dorsal skin for 16 h. After magnet removal, the animals received HBOT, daily on weekdays, for 4 weeks. To examine the effect of HBOT on diabetes impaired wound healing, the degree of wound tissue perfusion, inflammation, angiogenesis, and tissue breaking strength were evaluated. HBOT effects on the degree of inflammation and number of blood vessels could not be observed. HBOT improved the tissue breaking strength of the wound, however, this did not reach statistical significance. Twenty hours after ending the HBOT, a significantly improved oxygen saturation of the hemoglobin at the venous end of the capillaries and the quantity of hemoglobin in the micro-blood vessels was measured.

Diabetes-impaired wound healing is improved by matrix therapy with heparan sulfate glycosaminoglycan mimetic OTR4120 in rats.

Wound healing in diabetes is frequently impaired, and its treatment remains a challenge. We tested a therapeutic strategy of potentiating intrinsic tissue regeneration by restoring the wound cellular environment using a heparan sulfate glycosaminoglycan mimetic, OTR4120. The effect of OTR4120 on healing of diabetic ulcers was investigated. Experimental diabetes was induced by intraperitoneal injection of streptozotocin. Seven weeks after induction of diabetes, rats were ulcerated by clamping a pair of magnet disks on the dorsal skin for 16 h. After magnet removal, OTR4120 was administered via an intramuscular injection weekly for up to 4 weeks. To examine the effect of OTR4120 treatment on wound heal-ing, the degree of ulceration, inflammation, angiogenesis, and collagen synthesis were evaluated. We found that OTR4120 treatment significantly reduced the degree of ulceration and the time of healing. These effects were associated with reduced neutrophil infiltration and macrophage accumulation and enhanced angiogenesis. OTR4120 treatment also increased the collagen content with an increase of collagen type I biosynthesis and reduction of collagen type III biosynthesis. Moreover, restoration of the ulcer biomechanical strength was significantly enhanced after OTR4120 treatment. This study shows that matrix therapy with OTR4120 improves diabetes-impaired wound healing.