Hosseinzadeh Simzar, Shams Forough, Fattahi Roya, Nuoroozi Ghader, Rostami Elnaz, Shahghasempour Lida, Salehi-Nik Nasim, Bohlouli Mahboubeh, Khojasteh Arash, Ghasemi Nazanin, Peiravi Habibollah
Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Adv Pharm Bull. 2023 Jan;13(1):123-133. doi: 10.34172/apb.2023.013. Epub 2022 Jan 3.
A hemocompatible substrate can offer a wonderful facility for nitric oxide (NO) production by vascular endothelial cells in reaction to the inflammation following injuries. NO inhibits platelet aggregation this is especially critical in small-diameter vessels. The substrate films were made of polyurethane (PU) in a casting process and after plasma treatments, their surface was chemically decorated with polyethylene glycol (PEG) 2000, gelatin, gelatin-aspirin, gelatin-heparin and gelatin-aspirin-heparin. The concentrations of these ingredients were optimized in order to achieve the biocompatible values and the resulting modifications were characterized by water contact angle and Fourier transform infra-red (FTIR) assays. The values of NO production and platelet adhesion were then examined. The water contact angle of the modified surface was reduced to 26±4 and the newly developed hydrophilic chemical groups were confirmed by FTIR. The respective concentrations of 0.05 mg/ml and 100 mg/mL were found to be the IC50 values for aspirin and heparin. However, after the surface modification with aspirin, the bioactivity of the substrate increased in compared to the other experimental groups. In addition, there was a synergistic effect between these reagents for NO synthesis. While, heparin inhibited platelet adhesion more than aspirin. Because of the highly hydrophilic nature of heparin, this reagent was hydrolyzed faster than aspirin and therefore its influence on platelet aggregation and cell growth was greater. Taken together, the results give the biocompatible concentrations of both biomolecules that are required for endothelial cell proliferation, NO synthesis and platelet adhesion.
一种血液相容性基质可为血管内皮细胞在损伤后炎症反应中产生一氧化氮(NO)提供良好的条件。NO可抑制血小板聚集,这在小直径血管中尤为关键。基质膜是通过浇铸工艺由聚氨酯(PU)制成的,经过等离子体处理后,其表面用聚乙二醇(PEG)2000、明胶、明胶 - 阿司匹林、明胶 - 肝素和明胶 - 阿司匹林 - 肝素进行化学修饰。对这些成分的浓度进行了优化,以实现生物相容性值,并通过水接触角和傅里叶变换红外(FTIR)分析对所得修饰进行表征。然后检测了NO产生和血小板粘附的值。修饰表面的水接触角降低到26±4,FTIR证实了新形成的亲水性化学基团。发现阿司匹林和肝素的IC50值分别为0.05 mg/ml和100 mg/mL。然而,与其他实验组相比,用阿司匹林进行表面修饰后,基质的生物活性增加。此外,这些试剂在NO合成方面存在协同作用。同时,肝素比阿司匹林更能抑制血小板粘附。由于肝素具有高度亲水性,该试剂比阿司匹林水解得更快,因此其对血小板聚集和细胞生长的影响更大。综上所述,这些结果给出了内皮细胞增殖、NO合成和血小板粘附所需的两种生物分子的生物相容性浓度。