Pant Jitendra, Pedaparthi Shriya, Hopkins Sean P, Goudie Marcus J, Douglass Megan E, Handa Hitesh
School of Chemical, Materials, and Biomedical Engineering, University of Georgia, Athens, Georgia 30602, United States.
ACS Biomater Sci Eng. 2019 Aug 12;5(8):4002-4012. doi: 10.1021/acsbiomaterials.9b00737. Epub 2019 Jul 17.
Biological processes such as infection, angiogenesis, and fibroblast proliferation and migration need to be regulated for effective healing of a wound. Failing to do so can delay the overall wound healing and add to the suffering and healthcare cost. Endogenous nitric oxide (NO) is a well-known gasotransmitter in the natural healing process in humans and other mammals. To utilize its inherent ability in the current study, an exogenous NO donor (-nitroso-glutathione, GSNO) was integrated into a hybrid formulation consisting of a natural polymer (alginate) and a synthetic polymer (poly(vinyl alcohol) (PVA)). The alginate-PVA-GSNO dressings showed a sustained NO release for 72 h that resulted in 99.89 ± 0.40% and 98.93 ± 0.69% eradication of and , respectively, which are among the most common causal agents of wound infections. The designed dressings resulted in a 3-fold increase in the proliferation of human endothelial cells when compared with control without GSNO showing its angiogenic potential. In addition, mouse fibroblast cells exposed to leachates from alginate-PVA-GSNO dressings showed significantly higher proliferation when compared to control alginate-PVA showing the NO release from exogenous GSNO in fibroblast proliferation. Fibroblast migration was shown to be much faster with GSNO-based dressings when compared to corresponding control dressings resulting in complete closure of an in vitro wound model within 48 h. The porous dressings also possessed important physical properties such as swelling, water vapor transmission, and moisture content that are desirable for effective wound healing. Overall, this study supports the possibility of using therapeutic alginate-PVA-GSNO dressing to provide a supportive environment for accelerated wound healing.
为实现伤口的有效愈合,诸如感染、血管生成以及成纤维细胞增殖和迁移等生物过程需要得到调控。若未能如此,可能会延迟伤口的整体愈合,并增加患者的痛苦以及医疗成本。内源性一氧化氮(NO)是人类和其他哺乳动物自然愈合过程中一种广为人知的气体递质。为在当前研究中利用其内在能力,将一种外源性NO供体(-亚硝基谷胱甘肽,GSNO)整合到由天然聚合物(海藻酸盐)和合成聚合物(聚乙烯醇(PVA))组成的混合制剂中。海藻酸盐-PVA-GSNO敷料显示出持续72小时的NO释放,分别导致99.89±0.40%和98.93±0.69%的金黄色葡萄球菌和大肠杆菌被根除,它们是伤口感染最常见的致病因素。与不含GSNO的对照相比,所设计的敷料使人类内皮细胞的增殖增加了3倍,显示出其血管生成潜力。此外,与对照海藻酸盐-PVA相比,暴露于海藻酸盐-PVA-GSNO敷料浸出液的小鼠成纤维细胞显示出显著更高的增殖,表明外源性GSNO在成纤维细胞增殖中释放了NO。与相应的对照敷料相比,基于GSNO的敷料显示成纤维细胞迁移速度快得多,在48小时内使体外伤口模型完全闭合。这种多孔敷料还具有诸如膨胀、水蒸气透过率和水分含量等重要的物理性质,这些性质对于有效的伤口愈合是理想的。总体而言,本研究支持使用治疗性海藻酸盐-PVA-GSNO敷料为加速伤口愈合提供支持性环境的可能性。