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dc.contributor.authorLim, Natalie Sheng Jie-
dc.contributor.authorSham, Adeline-
dc.contributor.authorChee, Stella Min Ling-
dc.contributor.authorChan, Casey-
dc.contributor.authorRaghunath, Michael-
dc.date.accessioned2018-10-26T13:34:54Z-
dc.date.available2018-10-26T13:34:54Z-
dc.date.issued2016-
dc.identifier.issn1524-475Xde_CH
dc.identifier.urihttps://digitalcollection.zhaw.ch/handle/11475/12186-
dc.description.abstractGranulation tissue formation requires a robust angiogenic response. As granulation tissue develops, collagen fibers are deposited and compacted. Forces generated in the wake of this process drive wound contraction to reduce the wound area. In diabetics, both angiogenesis and wound contraction are diminished leading to impaired wound healing. To emulate this pathology and to address it pharmacologically, we developed a wound healing model in the diabetic Zucker fatty rat and tested a topical proangiogenic strategy combining antifungal agent ciclopirox olamine (CPX) and lysophospholipid sphingosine‐1‐phosphate (S1P) to promote diabetic wound closure. In vitro, we demonstrated that CPX + S1P up‐regulates a crucial driver of angiogenesis, hypoxia‐inducible factor‐1, in endothelial cells. Injection of CPX + S1P into subcutaneously implanted sponges in experimental rats showed, in an additive manner, a fivefold increased endothelial infiltration and lectin‐perfused vessel length. We developed a splinted diabetic rodent model to achieve low wound contraction rates that are characteristic for the healing mode of diabetic ulcers in humans. We discovered specific dorsal sites that allowed for incremental full‐thickness excisional wound depths from 1 mm (superficial) to 3 mm (deep). This enabled us to bring down wound contraction from 51% in superficial wounds to 8% in deep wounds. While the effects of topical gel treatment of CPX + S1P were masked by the rodent‐characteristic dominant contraction in superficial wounds, they became clearly evident in deep diabetic wounds. Here, a fivefold increase of functional large vessels resulted in accelerated granulation tissue formulation, accompanied by a 40% increase of compacted thick collagen fibers. This was associated with substantially reduced matrix metalloproteinase‐3 and ‐13 expression. These findings translated into a fivefold increase in granulation‐driven contraction, promoting diabetic wound closure. With CPX and S1P analogues already in clinical use, their combination presents itself as an attractive proangiogenic treatment to be repurposed for diabetic wound healing.de_CH
dc.language.isoende_CH
dc.publisherWileyde_CH
dc.relation.ispartofWound Repair and Regenerationde_CH
dc.rightsLicence according to publishing contractde_CH
dc.subject.ddc571: Physiologie und verwandte Themende_CH
dc.subject.ddc617: Chirurgiede_CH
dc.titleCombination of ciclopirox olamine and sphingosine-1-phosphate as granulation enhancer in diabetic woundsde_CH
dc.typeBeitrag in wissenschaftlicher Zeitschriftde_CH
dcterms.typeTextde_CH
zhaw.departementLife Sciences und Facility Managementde_CH
zhaw.organisationalunitInstitut für Chemie und Biotechnologie (ICBT)de_CH
dc.identifier.doi10.1111/wrr.12463de_CH
zhaw.funding.euNode_CH
zhaw.issue5de_CH
zhaw.originated.zhawNode_CH
zhaw.pages.end809de_CH
zhaw.pages.start795de_CH
zhaw.publication.statuspublishedVersionde_CH
zhaw.volume24de_CH
zhaw.publication.reviewPeer review (Publikation)de_CH
zhaw.webfeedMetabolic Tissue Engineeringde_CH
Appears in collections:Publikationen Life Sciences und Facility Management

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Lim, N. S. J., Sham, A., Chee, S. M. L., Chan, C., & Raghunath, M. (2016). Combination of ciclopirox olamine and sphingosine-1-phosphate as granulation enhancer in diabetic wounds. Wound Repair and Regeneration, 24(5), 795–809. https://doi.org/10.1111/wrr.12463
Lim, N.S.J. et al. (2016) ‘Combination of ciclopirox olamine and sphingosine-1-phosphate as granulation enhancer in diabetic wounds’, Wound Repair and Regeneration, 24(5), pp. 795–809. Available at: https://doi.org/10.1111/wrr.12463.
N. S. J. Lim, A. Sham, S. M. L. Chee, C. Chan, and M. Raghunath, “Combination of ciclopirox olamine and sphingosine-1-phosphate as granulation enhancer in diabetic wounds,” Wound Repair and Regeneration, vol. 24, no. 5, pp. 795–809, 2016, doi: 10.1111/wrr.12463.
LIM, Natalie Sheng Jie, Adeline SHAM, Stella Min Ling CHEE, Casey CHAN und Michael RAGHUNATH, 2016. Combination of ciclopirox olamine and sphingosine-1-phosphate as granulation enhancer in diabetic wounds. Wound Repair and Regeneration. 2016. Bd. 24, Nr. 5, S. 795–809. DOI 10.1111/wrr.12463
Lim, Natalie Sheng Jie, Adeline Sham, Stella Min Ling Chee, Casey Chan, and Michael Raghunath. 2016. “Combination of Ciclopirox Olamine and Sphingosine-1-Phosphate as Granulation Enhancer in Diabetic Wounds.” Wound Repair and Regeneration 24 (5): 795–809. https://doi.org/10.1111/wrr.12463.
Lim, Natalie Sheng Jie, et al. “Combination of Ciclopirox Olamine and Sphingosine-1-Phosphate as Granulation Enhancer in Diabetic Wounds.” Wound Repair and Regeneration, vol. 24, no. 5, 2016, pp. 795–809, https://doi.org/10.1111/wrr.12463.


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