Elgharably Haytham, Ganesh Kasturi, Dickerson Jennifer, Khanna Savita, Abas Motaz, Ghatak Piya Das, Dixit Sriteja, Bergdall Valerie, Roy Sashwati, Sen Chandan K
Department of Surgery, Davis Heart & Lung Research Institute, Center for Regenerative Medicine and Cell Based Therapies, Comprehensive Wound Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Wound Repair Regen. 2014 Nov-Dec;22(6):720-9. doi: 10.1111/wrr.12229. Epub 2015 Jan 8.
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 bipedicle 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 interleukin (IL)-10 and of fibroblast growth factor-basic (β-FGF). An increased expression of CCR2, an 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 transforming growth factor-β, vascular endothelial growth factor, von Willebrand's factor, 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 that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds.
我们最近对一种改良胶原蛋白凝胶（MCG）敷料进行了蛋白质组学表征，并报告了该凝胶在全层切除伤口愈合方面的良好效果。在这项工作中，我们通过在我们实验室最近报道的慢性缺血性伤口猪模型中测试该敷料，来检验上述发现的转化相关性。在动物背部的双蒂缺血性皮瓣中心建立全层切除伤口。通过激光多普勒成像验证缺血情况，并将MCG应用于伤口测试组。受伤7天后，MCG处理的缺血性伤口中巨噬细胞向伤口的募集明显更高。在体外，MCG上调了Mrc-1（一种修复性M2巨噬细胞标志物）的表达，并诱导了抗炎细胞因子白细胞介素（IL）-10和成纤维细胞生长因子-碱性（β-FGF）的表达。在来自MCG处理伤口的巨噬细胞中，注意到M2巨噬细胞标志物CCR2的表达增加。此外，受伤7天后对伤口组织的分析显示，MCG处理的缺血性伤口中转化生长因子-β、血管内皮生长因子、血管性血友病因子和I型胶原蛋白表达上调。受伤21天后，MCG处理的缺血性伤口显示出形成成熟血管结构的增殖内皮细胞数量增加，伤口血流量增加。MCG处理的缺血性伤口边缘组织中的成纤维细胞计数明显更高。此外，MCG处理的伤口边缘组织显示出成熟胶原蛋白的丰度更高，I型：III型胶原蛋白沉积增加。综上所述，MCG有助于引发更强烈的炎症反应，该反应能及时消退，随后是增殖期增强、血管生成结果改善和伤口后组织重塑。本研究结果值得在缺血性慢性伤口环境中对MCG进行临床试验。
