Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut Health, Farmington 06030, CT, USA.
Stanley J. Dudrick, Department of Surgery, Saint Mary's Hospital, Waterbury 06706, CT, USA.
Int J Pharm. 2019 Mar 10;558:177-186. doi: 10.1016/j.ijpharm.2019.01.001. Epub 2019 Jan 9.
The complete loss of dermal tissue due to ischemia is a serious challenge facing clinicians. Frequently, the failure of wound healing is due to ischemic conditions prevailing at the site of damaged tissue. Restoration of lost vasculature at the ischemic site can be achieved by supplementing proangiogenic stimuli through an engineered scaffold mimicking dermal extracellular matrix. Towards this objective, we have developed an electrospun scaffold loaded with the pro-angiogenic molecule resveratrol. The physical and chemical changes in the polymeric scaffold before and after loading of resveratrol were characterized using field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), coherence scanning interferometry (CSI) and X-ray diffraction (XRD). A sustained release of resveratrol from the scaffold was elucidated by UV-spectrophotometer analysis. The enhancement in cell-matrix interaction was studied using human umbilical vein endothelial cells (HUVECs) seeded on the scaffolds. The biocompatibility analysis of resveratrol loaded scaffolds was evaluated through a subcutaneous implantation study in mice. The therapeutic potential of resveratrol loaded scaffolds to accelerate tissue repair was analyzed in a full-thickness ischemic wound model in mice. Wound closure and H&E staining analysis showed rapid closure of ischemic wound area and re-epithelialization in resveratrol loaded scaffold treated groups compared to collagen and negative control groups. The immunostaining analysis further revealed the activation of thioredoxin-1 (Trx-1), heme oxygenase-1 (HO-1) mediated vascular endothelial growth factor (VEGF) signaling in resveratrol loaded scaffold treated group. The expression of Bcl-2 in healing wound edges post-treatment with resveratrol loaded scaffold confirmed the anti-apoptotic effect mediated by resveratrol. From this study, we explored a synergistic effect mediated by resveratrol and fibrous scaffolds to aid the ischemic wound healing process through effective vascularization.
由于缺血导致的皮肤组织完全丧失是临床医生面临的一个严重挑战。通常，伤口愈合失败是由于受损组织部位存在缺血情况。通过在模拟真皮细胞外基质的工程支架中补充促血管生成刺激物，可以实现缺血部位丢失的脉管系统的重建。为了实现这一目标，我们开发了一种负载促血管生成分子白藜芦醇的静电纺丝支架。使用场发射扫描电子显微镜 (FE-SEM)、傅里叶变换红外光谱 (FT-IR)、差示扫描量热法 (DSC)、热重分析 (TGA)、相干扫描干涉测量法 (CSI) 和 X 射线衍射 (XRD) 对负载白藜芦醇前后聚合物支架的物理和化学变化进行了表征。通过紫外分光光度计分析阐明了支架中白藜芦醇的持续释放。通过在支架上接种人脐静脉内皮细胞 (HUVEC) 研究细胞与基质的相互作用增强。通过在小鼠中进行皮下植入研究评估负载白藜芦醇支架的生物相容性分析。通过在小鼠全层缺血性伤口模型中分析负载白藜芦醇支架加速组织修复的治疗潜力。伤口闭合和 H&E 染色分析表明，与胶原和阴性对照组相比，负载白藜芦醇支架处理组的缺血性伤口区域迅速闭合和再上皮化。免疫染色分析进一步揭示了负载白藜芦醇支架处理组中硫氧还蛋白-1 (Trx-1)、血红素加氧酶-1 (HO-1) 介导的血管内皮生长因子 (VEGF) 信号的激活。负载白藜芦醇支架治疗后愈合伤口边缘的 Bcl-2 表达证实了白藜芦醇介导的抗细胞凋亡作用。通过这项研究，我们探索了白藜芦醇和纤维支架介导的协同作用，通过有效的血管生成来辅助缺血性伤口愈合过程。
