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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 hea...

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Autores principales: Tong, Miao, Tuk, Bastiaan, Shang, Peng, Hekking, Ineke M., Fijneman, Esther M.G., Guijt, Marnix, Hovius, Steven E.R., van Neck, Johan W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447910/
https://www.ncbi.nlm.nih.gov/pubmed/22721969
http://dx.doi.org/10.2337/db11-1329
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author Tong, Miao
Tuk, Bastiaan
Shang, Peng
Hekking, Ineke M.
Fijneman, Esther M.G.
Guijt, Marnix
Hovius, Steven E.R.
van Neck, Johan W.
author_facet Tong, Miao
Tuk, Bastiaan
Shang, Peng
Hekking, Ineke M.
Fijneman, Esther M.G.
Guijt, Marnix
Hovius, Steven E.R.
van Neck, Johan W.
author_sort Tong, Miao
collection PubMed
description 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.
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spelling pubmed-34479102013-10-01 Diabetes-Impaired Wound Healing Is Improved by Matrix Therapy With Heparan Sulfate Glycosaminoglycan Mimetic OTR4120 in Rats Tong, Miao Tuk, Bastiaan Shang, Peng Hekking, Ineke M. Fijneman, Esther M.G. Guijt, Marnix Hovius, Steven E.R. van Neck, Johan W. Diabetes Pharmacology and Therapeutics 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. American Diabetes Association 2012-10 2012-09-13 /pmc/articles/PMC3447910/ /pubmed/22721969 http://dx.doi.org/10.2337/db11-1329 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Pharmacology and Therapeutics
Tong, Miao
Tuk, Bastiaan
Shang, Peng
Hekking, Ineke M.
Fijneman, Esther M.G.
Guijt, Marnix
Hovius, Steven E.R.
van Neck, Johan W.
Diabetes-Impaired Wound Healing Is Improved by Matrix Therapy With Heparan Sulfate Glycosaminoglycan Mimetic OTR4120 in Rats
title Diabetes-Impaired Wound Healing Is Improved by Matrix Therapy With Heparan Sulfate Glycosaminoglycan Mimetic OTR4120 in Rats
title_full Diabetes-Impaired Wound Healing Is Improved by Matrix Therapy With Heparan Sulfate Glycosaminoglycan Mimetic OTR4120 in Rats
title_fullStr Diabetes-Impaired Wound Healing Is Improved by Matrix Therapy With Heparan Sulfate Glycosaminoglycan Mimetic OTR4120 in Rats
title_full_unstemmed Diabetes-Impaired Wound Healing Is Improved by Matrix Therapy With Heparan Sulfate Glycosaminoglycan Mimetic OTR4120 in Rats
title_short Diabetes-Impaired Wound Healing Is Improved by Matrix Therapy With Heparan Sulfate Glycosaminoglycan Mimetic OTR4120 in Rats
title_sort diabetes-impaired wound healing is improved by matrix therapy with heparan sulfate glycosaminoglycan mimetic otr4120 in rats
topic Pharmacology and Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447910/
https://www.ncbi.nlm.nih.gov/pubmed/22721969
http://dx.doi.org/10.2337/db11-1329
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