A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds.

A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds.
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DOI:
10.1111/wrr.12229
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发表时间:
2014-11
期刊:
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
影响因子:
--
通讯作者:
Sen CK
Sen CK
中科院分区:
其他
文献类型:
--
作者:
Elgharably H;Ganesh K;Dickerson J;Khanna S;Abas M;Ghatak PD;Dixit S;Bergdall V;Roy S;Sen CK

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我们最近对改良胶原凝胶(MCG)敷料进行了蛋白质组学表征,并报告了凝胶在愈合全层切除伤口方面的良好效果。在这项工作中,我们通过在我们实验室最近报告的慢性缺血性伤口猪模型中测试敷料来测试我们上述发现的翻译相关性。在动物背部双蒂缺血皮瓣中心建立全层切除创面。激光多普勒成像证实缺血,并对试验组伤口进行MCG。创伤后7天,MCG处理的缺血性伤口中巨噬细胞向伤口的募集显著更高。在体外,MCG上调Mrc-1(一种修复性M2巨噬细胞标志物)的表达,并诱导抗炎细胞因子IL-10和β-FGF的表达。在来自MCG处理的伤口的巨噬细胞中注意到M2巨噬细胞标志物CCR 2的表达增加。此外,对创伤后7天的伤口组织的分析显示,在MCG处理的缺血性伤口中,TGF-β、VEGF、vWF和I型胶原蛋白表达上调。在创伤后21天,MCG治疗的缺血性伤口显示出更高丰度的增殖内皮细胞,其形成成熟的血管结构并增加流向伤口的血流量。成纤维细胞计数在MCG治疗的缺血性伤口边缘组织中明显更高。此外,MCG处理的伤口边缘组织显示出更高丰度的成熟胶原蛋白,并增加I型胶原蛋白:III型胶原蛋白沉积。总之,MCG有助于建立更强大的炎症反应,及时解决,随后是增强的增殖期,血管生成结果和创伤后组织重塑。目前研究的结果证明了MCG在缺血性慢性伤口中的临床试验。
We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full thickness excisional wounds were established in the center of bi- pedicle ischemic skin flaps on the backs of animals. Ischemia was verified by Laser Doppler imaging and MCG was applied to the test group of wounds. Seven days post- wounding, macrophage recruitment to the wound was significantly higher in MCG- treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine IL-10 and of β-FGF. An increased expression of CCR2, a M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of TGF-β, VEGF, vWF, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post-wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I:III deposition. Taken together, MCG helped mount a more robust inflammatory response which resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome and post-wound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds.
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