Abstract |
Pressure ulcers are a major clinical problem, with a large burden on healthcare resources. This study evaluated the effects of the heparan sulfate glycosaminoglycan mimetic, OTR4120, on pressure ulceration and healing. Ischemia-reperfusion (I-R) was evoked to induce pressure ulcers by external clamping and then removal of a pair of magnet disks on rat dorsal skin for a single ischemic period of 16 hours. Immediately after magnet removal, rats received an intramuscular injection of OTR4120 weekly for up to 1 month. During the ischemic period, normal skin perfusion was reduced by at least 60% and at least 20-45% reperfused into the ischemic region after compression release. This model caused sustained skin incomplete necrosis for up to 14 days and led to grade 2-3 ulcers. OTR4120 treatment decreased the area of skin incomplete necrosis and degree of ulceration. OTR4120 treatment also reduced inflammation and increased angiogenesis. In OTR4120-treated ulcers, the contents of vascular endothelial growth factor, platelet-derived growth factor, and transforming growth factor beta-1 were increased. Moreover, OTR4120 treatment promoted early expression of alpha-smooth muscle actin and increased collagen biosynthesis. Long-term restoration of wounded tissue biomechanical strength was significantly enhanced after OTR4120 treatment. Taken together, we conclude that OTR4120 treatment reduces pressure ulcer formation and potentiates the internal healing bioavailability.
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Authors | Miao Tong, Bastiaan Tuk, Ineke M Hekking, Mieke M Pleumeekers, Mireille B Boldewijn, Steven E R Hovius, Johan W van Neck |
Journal | Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
(Wound Repair Regen)
2011 Jul-Aug
Vol. 19
Issue 4
Pg. 505-14
ISSN: 1524-475X [Electronic] United States |
PMID | 21649786
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2011 by the Wound Healing Society. |
Chemical References |
- Actins
- Glycosaminoglycans
- OTR4120
- Platelet-Derived Growth Factor
- Transforming Growth Factor beta1
- Vascular Endothelial Growth Factor A
- smooth muscle actin, rat
- Collagen
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Topics |
- Actins
(metabolism)
- Animals
- Biomechanical Phenomena
- Collagen
(biosynthesis)
- Disease Models, Animal
- Female
- Glycosaminoglycans
(pharmacology)
- Inflammation
(drug therapy)
- Injections, Intramuscular
- Neovascularization, Physiologic
(drug effects)
- Platelet-Derived Growth Factor
(metabolism)
- Pressure Ulcer
(therapy)
- Rats
- Reperfusion Injury
- Transforming Growth Factor beta1
(metabolism)
- Vascular Endothelial Growth Factor A
(metabolism)
- Wound Healing
(drug effects)
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