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PVA/Dextran 水凝胶贴片作为抗氧化剂虾青素的递送系统:心血管方法。

PVA/Dextran hydrogel patches as delivery system of antioxidant astaxanthin: a cardiovascular approach.

机构信息

INSERM, U1148, Laboratory for Vascular Translational Science, Cardiovascular Bioengineering, Paris 13 University, Sorbonne Paris Cite 99, Av. Jean-Baptiste Clément, F-93430 Villetaneuse, France. INSERM, U1148, Laboratory for Vascular Translational Science, Cardiovascular Bioengineering, CHU X. Bichat, 46 rue H. Huchard, F-75018 Paris, France.

出版信息

Biomed Mater. 2017 Dec 28;13(1):015020. doi: 10.1088/1748-605X/aa8a86.

Abstract

After myocardial infarction, the heart's mechanical properties and its intrinsic capability to recover are compromised. To improve this recovery, several groups have developed cardiac patches based on different biomaterials strategies. Here, we developed polyvinylalcohol/dextran (PVA/Dex) elastic hydrogel patches, obtained through the freeze thawing (FT) process, with the aim to deliver locally a potent natural antioxidant molecule, astaxanthin, and to assist the heart's response against the generated myofibril stress. Extensive rheological and dynamo-mechanical characterization of the effect of the PVA molecular weight, number of freeze-thawing cycles and Dex addition on the mechanical properties of the resulting hydrogels, were carried out. Hydrogel systems based on PVA 145 kDa and PVA 47 kDa blended with Dex 40 kDa, were chosen as the most promising candidates for this application. In order to improve astaxanthin solubility, an inclusion system using hydroxypropyl-β-cyclodextrin was prepared. This system was posteriorly loaded within the PVA/Dex hydrogels. PVA145/Dex 1FT and PVA47/Dex 3FT showed the best rheological and mechanical properties when compared to the other studied systems; environmental scanning electron microscope and confocal imaging evidenced a porous structure of the hydrogels allowing astaxanthin release. In vitro cellular behavior was analyzed after 24 h of contact with astaxanthin-loaded hydrogels. In vivo subcutaneous biocompatibility was performed in rats using PVA145/Dex 1FT, as the best compromise between mechanical support and astaxanthin delivery. Finally, ex vivo and in vivo experiments showed good mechanical and compatibility properties of this hydrogel. The obtained results showed that the studied materials have a potential to be used as myocardial patches to assist infarcted heart mechanical function and to reduce oxidative stress by the in situ release of astaxanthin.

摘要

心肌梗死后,心脏的机械性能及其内在的恢复能力受损。为了改善这种恢复,有几个小组已经开发了基于不同生物材料策略的心脏补片。在这里,我们开发了基于聚乙烯醇/葡聚糖(PVA/Dex)的弹性水凝胶补片,通过冷冻-解冻(FT)过程获得,目的是局部递送一种有效的天然抗氧化分子虾青素,并帮助心脏应对产生的肌原纤维应激。我们对 PVA 分子量、冻融循环次数和 Dex 添加对所得水凝胶机械性能的影响进行了广泛的流变和动力机械特性研究。基于 PVA 145 kDa 和 PVA 47 kDa 与 Dex 40 kDa 混合的水凝胶系统被选为该应用的最有前途的候选物。为了提高虾青素的溶解度,制备了使用羟丙基-β-环糊精的包合系统。该系统随后被加载到 PVA/Dex 水凝胶中。与其他研究系统相比,PVA145/Dex 1FT 和 PVA47/Dex 3FT 显示出更好的流变学和力学性能;环境扫描电子显微镜和共焦成像表明水凝胶具有多孔结构,允许虾青素释放。在与负载虾青素的水凝胶接触 24 小时后分析了体外细胞行为。在大鼠中进行了皮下生物相容性的体内实验,使用 PVA145/Dex 1FT,作为机械支撑和虾青素递送之间的最佳折衷。最后,离体和体内实验表明这种水凝胶具有良好的机械和相容性。研究结果表明,所研究的材料具有作为心肌补片的潜力,可用于辅助梗死心脏的机械功能,并通过原位释放虾青素来减少氧化应激。

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