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用于肺修复的基于抗癌治疗的海藻酸盐组织密封剂。

Anticancer Therapeutic Alginate-Based Tissue Sealants for Lung Repair.

机构信息

Department of Biomedical Engineering, Tufts University , Medford, Massachusetts 02155, United States.

Bioengineering Program, College of Engineering and Mathematical Sciences, and Larner College of Medicine, University of Vermont , Burlington, Vermont 05405, United States.

出版信息

ACS Appl Mater Interfaces. 2017 Jul 19;9(28):23409-23419. doi: 10.1021/acsami.7b04932. Epub 2017 Jul 6.

DOI:10.1021/acsami.7b04932
PMID:28648052
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5546308/
Abstract

Injury to the connective tissue that lines the lung, the pleura, or the lung itself can occur from many causes including trauma or surgery, as well as lung diseases or cancers. To address current limitations for patching lung injuries, to stop air or fluid leaks, an adherent hydrogel sealant patch system was developed, based on methacrylated alginate (AMA) and AMA dialdehyde (AMA-DA) blends, which is capable of sealing damaged tissues and sustaining physiological pressures. Methacrylation of alginate hydroxyl groups rendered the polysaccharide capable of photo-cross-linking when mixed with an eosin Y-based photoinitiator system and exposed to visible green light. Oxidation of alginate yields functional aldehyde groups capable of imine bond formation with proteins found in many tissues. The alginate-based patch system was rigorously tested on a custom burst pressure testing device. Blending of nonoxidized material with oxidized (aldehyde modified) alginates yielded patches with improved burst pressure performance and decreased delamination as compared with pure AMA. Human mesothelial cell (MeT-5A) viability and cytotoxicity were retained when cultured with the hydrogel patches. The release and bioactivity of doxorubicin-encapsulated submicrospheres enabled the fabrication of drug-eluting adhesive patches and were effective in decreasing human lung cancer cell (A549) viability.

摘要

肺、胸膜或肺本身的衬里结缔组织损伤可能由多种原因引起,包括创伤或手术,以及肺部疾病或癌症。为了解决目前在修补肺损伤、阻止空气或液体泄漏方面的局限性,开发了一种基于甲基丙烯酰化藻酸盐(AMA)和 AMA 二醛(AMA-DA)混合物的粘附性水凝胶密封贴片系统,它能够密封受损组织并维持生理压力。藻酸盐的羟基甲基化使多糖在与基于曙红 Y 的光引发剂系统混合并暴露于可见光绿光时能够光交联。藻酸盐的氧化产生了功能性醛基,能够与许多组织中发现的蛋白质形成亚胺键。基于藻酸盐的贴片系统在定制的破裂压力测试设备上进行了严格测试。与纯 AMA 相比,未氧化材料与氧化(醛修饰)藻酸盐的混合使贴片的破裂压力性能提高,分层减少。当与人胸膜间皮细胞(MeT-5A)共培养时,水凝胶贴片保留了细胞活力和细胞毒性。载阿霉素亚微球的释放和生物活性使可载药的粘附贴片得以制备,并有效降低了人肺癌细胞(A549)的活力。

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