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.

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.

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.

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