| Publikationstyp: | Beitrag in wissenschaftlicher Zeitschrift |
| Art der Begutachtung: | Peer review (Publikation) |
| Titel: | Combination of ciclopirox olamine and sphingosine-1-phosphate as granulation enhancer in diabetic wounds |
| Autor/-in: | Lim, Natalie Sheng Jie Sham, Adeline Chee, Stella Min Ling Chan, Casey Raghunath, Michael |
| DOI: | 10.1111/wrr.12463 |
| Erschienen in: | Wound Repair and Regeneration |
| Band(Heft): | 24 |
| Heft: | 5 |
| Seite(n): | 795 |
| Seiten bis: | 809 |
| Erscheinungsdatum: | 2016 |
| Verlag / Hrsg. Institution: | Wiley |
| ISSN: | 1524-475X |
| Sprache: | Englisch |
| Fachgebiet (DDC): | 571: Physiologie und verwandte Themen 617: Chirurgie |
| Zusammenfassung: | Granulation 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. |
| URI: | https://digitalcollection.zhaw.ch/handle/11475/12186 |
| Volltext Version: | Publizierte Version |
| Lizenz (gemäss Verlagsvertrag): | Lizenz gemäss Verlagsvertrag |
| Departement: | Life Sciences und Facility Management |
| Organisationseinheit: | Institut für Chemie und Biotechnologie (ICBT) |
| Enthalten in den Sammlungen: | Publikationen Life Sciences und Facility Management |
Dateien zu dieser Ressource:
Es gibt keine Dateien zu dieser Ressource.
Zur Langanzeige
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.
Alle Ressourcen in diesem Repository sind urheberrechtlich geschützt, soweit nicht anderweitig angezeigt.