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血管生成肽纳米纤维促进链脲佐菌素诱导的糖尿病大鼠伤口愈合

Angiogenic Peptide Nanofibers Improve Wound Healing in STZ-Induced Diabetic Rats.

作者信息

Senturk Berna, Mercan Sercan, Delibasi Tuncay, Guler Mustafa O, Tekinay Ayse B

机构信息

Institute of Materials Science and Nanotechnology, National Nanotechnology Research Center (UNAM), Bilkent University, Ankara 06800, Turkey.

Department of Endocrinology and Metabolism, ADACELL Cell Therapy, Regenerative Medicine and Research Hospital Etlik Polyclinic, Ankara, 06010, Turkey.

出版信息

ACS Biomater Sci Eng. 2016 Jul 11;2(7):1180-1189. doi: 10.1021/acsbiomaterials.6b00238. Epub 2016 Jun 16.

Abstract

Low expressions of angiogenic growth factors delay the healing of diabetic wounds by interfering with the process of blood vessel formation. Heparin mimetic peptide nanofibers can bind to and enhance production and activity of major angiogenic growth factors, including VEGF. In this study, we showed that heparin mimetic peptide nanofibers can serve as angiogenic scaffolds that allow slow release of growth factors and protect them from degradation, providing a new therapeutic way to accelerate healing of diabetic wounds. We treated wounds in STZ-induced diabetic rats with heparin mimetic peptide nanofibers and studied repair of full-thickness diabetic skin wounds. Wound recovery was quantified by analyses of re-epithelialization, granulation tissue formation and blood vessel density, as well as VEGF and inflammatory response measurements. Wound closure and granulation tissue formation were found to be significantly accelerated in heparin mimetic gel treated groups. In addition, blood vessel counts and the expressions of alpha smooth muscle actin and VEGF were significantly higher in bioactive gel treated animals. These results strongly suggest that angiogenic heparin mimetic nanofiber therapy can be used to support the impaired healing process in diabetic wounds.

摘要

血管生成生长因子的低表达通过干扰血管形成过程而延迟糖尿病伤口的愈合。肝素模拟肽纳米纤维可结合并增强包括血管内皮生长因子(VEGF)在内的主要血管生成生长因子的产生和活性。在本研究中,我们表明肝素模拟肽纳米纤维可作为血管生成支架,使生长因子缓慢释放并保护它们不被降解,为加速糖尿病伤口愈合提供了一种新的治疗方法。我们用肝素模拟肽纳米纤维治疗链脲佐菌素诱导的糖尿病大鼠的伤口,并研究全层糖尿病皮肤伤口的修复情况。通过分析再上皮化、肉芽组织形成和血管密度以及VEGF和炎症反应测量来量化伤口恢复情况。发现肝素模拟凝胶治疗组的伤口闭合和肉芽组织形成明显加快。此外,生物活性凝胶治疗动物的血管计数以及α平滑肌肌动蛋白和VEGF的表达明显更高。这些结果有力地表明,血管生成性肝素模拟纳米纤维疗法可用于支持糖尿病伤口受损的愈合过程。

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