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Combining Biologically Active β-Lactams Integrin Agonists with Poly(l-lactic acid) Nanofibers: Enhancement of Human Mesenchymal Stem Cell Adhesion.
Biomacromolecules ( IF 6.2 ) Pub Date : 2020-02-14 , DOI: 10.1021/acs.biomac.9b01550
Giulia Martelli 1 , Nora Bloise 2, 3 , Andrea Merlettini 1 , Giovanna Bruni 4 , Livia Visai 2, 3 , Maria Letizia Focarete 1 , Daria Giacomini 1
Affiliation  

Regulating stem cell adhesion and growth onto functionalized biomaterial scaffolds is an important issue in the field of tissue engineering and regenerative medicine. In this study, new electrospun scaffolds of poly(l-lactic acid) (PLLA), as bioresorbable polymer, and β-lactam compounds agonists of selected integrins, as functional components with cell adhesive properties, are designed. The new β-lactam-PLLA scaffolds contribute significantly in guiding protein translation involved in human bone marrow mesenchymal stem cells (hBM-MSC) adhesion and integrin gene expression. Scanning electron microscopy, confocal laser scanning microscopy, and Western Blot analyses reveal that GM18-PLLA shows the best results, promoting cell adhesion by significantly driving changes in focal adhesion proteins distribution (β1 integrin and vinculin) and activation (pFAK), with a notable increase of GM18-targets subunits integrin gene expression, α4 and β1. These novel functionalized submicrometric fibrous scaffolds demonstrate, for the first time, the powerful combination of selective β-lactams agonists of integrins with biomimetic scaffolds, suggesting a designed rule that could be suitably applied to tissue repair and regeneration.

中文翻译:

结合生物活性β-内酰胺整联蛋白激动剂与聚(l-乳酸)纳米纤维:人间充质干细胞粘附的增强。

调节干细胞在功能化生物材料支架上的粘附和生长是组织工程和再生医学领域的重要问题。在这项研究中,设计了新型的可生物吸收聚合物的聚(l-乳酸)(PLLA)电纺丝支架,以及所选整合素的β-内酰胺化合物激动剂,作为具有细胞粘附特性的功能性成分。新的β-内酰胺-PLLA支架在指导人骨髓间充质干细胞(hBM-MSC)粘附和整联蛋白基因表达中所涉及的蛋白质翻译中起着重要作用。扫描电子显微镜,共聚焦激光扫描显微镜和Western Blot分析显示GM18-PLLA显示出最佳结果,通过显着驱动黏着斑蛋白分布(β1整联蛋白和vincorin)和激活(pFAK)的变化来促进细胞黏附,GM18靶标亚基整联蛋白基因表达α4和β1显着增加。这些新颖的功能化的亚微米级纤维支架首次证明了整联蛋白的选择性β-内酰胺类激动剂与仿生支架的强大组合,提出了可适用于组织修复和再生的设计规则。
更新日期:2020-02-14
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