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新型 3D 打印透明质酸甲基丙烯酸缩水甘油酯水凝胶支架的黏附性、抗炎和促血管生成特性分析及其在组织工程中的应用。

and Analysis of Adhesive, Anti-Inflammatory, and Proangiogenic Properties of Novel 3D Printed Hyaluronic Acid Glycidyl Methacrylate Hydrogel Scaffolds for Tissue Engineering.

机构信息

Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany.

Institute of Photon Technologies of Federal Scientific Research Centre "Crystallography and Photonics" of Russian Academy of Sciences, 108840 Moscow, Russia.

出版信息

ACS Biomater Sci Eng. 2020 Oct 12;6(10):5744-5757. doi: 10.1021/acsbiomaterials.0c00741. Epub 2020 Sep 8.

Abstract

In this study, we prepared hydrogel scaffolds for tissue engineering by computer-assisted extrusion three-dimensional (3D) printing with photocured (λ = 445 nm) hyaluronic acid glycidyl methacrylate (HAGM). The developed product was compared with the polylactic--glycolic acid (PLGA) scaffolds generated by means of the original antisolvent 3D printing methodology. The cytotoxicity and cytocompatibility of the scaffolds were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tests, flow cytometry, and scanning electron microscopy. Anti-inflammatory and proangiogenic properties of the scaffolds were evaluated in the dorsal skinfold chamber mouse model by means of intravital fluorescence microscopy, histology, and immunohistochemistry throughout an observation period of 14 days. , none of the scaffolds revealed cytotoxicity on days 1, 2, and 5 after seeding with umbilical cord-derived multipotent stromal cells, and the primary cell adhesion to the surface of HAGM scaffolds was low. , implanted HAGM scaffolds showed enhanced vascularization and host tissue ingrowth, and the inflammatory response to them was less pronounced compared with PLGA scaffolds. The results indicate excellent biocompatibility and vascularization capacity of the developed 3D printed HAGM scaffolds and position them as strong candidates for advanced tissue engineering applications.

摘要

在这项研究中,我们通过计算机辅助挤出三维(3D)打印技术,用光固化(λ=445nm)的透明质酸甲基丙烯酰基(HAGM)制备了水凝胶支架用于组织工程。所开发的产品与通过原始抗溶剂 3D 打印方法生成的聚乳酸-乙醇酸共聚物(PLGA)支架进行了比较。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴化物试验、流式细胞术和扫描电子显微镜分析了支架的细胞毒性和细胞相容性。通过在体荧光显微镜、组织学和免疫组织化学,在背部皮瓣室小鼠模型中评估了支架的抗炎和促血管生成特性,观察期为 14 天。结果表明,在接种脐带间充质干细胞后的第 1、2 和 5 天,没有支架显示出细胞毒性,并且 HAGM 支架表面的原始细胞黏附率较低。与 PLGA 支架相比,植入的 HAGM 支架显示出增强的血管生成和宿主组织内生长,并且对其的炎症反应不那么明显。结果表明,所开发的 3D 打印 HAGM 支架具有优异的生物相容性和血管生成能力,使其成为先进组织工程应用的有力候选者。

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