Current therapeutic interventions in bone defects are mainly focused on finding the best bioactive materials for inducing bone regeneration via activating the related intracellular signaling pathways. Integrins are trans‐membrane receptors that facilitate cell‐extracellular matrix (ECM) interactions and activate signal transduction. To develop a suitable platform for supporting human bone marrow mesenchymal stem cells (hBM‐MSCs) differentiation into bone tissue, electrospun poly L‐lactide (PLLA) nanofiber scaffolds were coated with nano‐hydroxyapatite (PLLA/nHa group), gelatin nanoparticles (PLLA/Gel group), and nHa/Gel nanoparticles (PLLA/nHa/Gel group) and their impacts on cell proliferation, expression of osteoblastic biomarkers, and bone differentiation were examined and compared. MTT data showed that proliferation of hBM‐MSCs on PLLA/nHa/Gel scaffolds was significantly higher than other groups (P < .05). Alkaline phosphatase activity was also more increased in hBM‐MSCs cultured under osteogenic media on PLLA/nHa/Gel scaffolds compared to others. Gene expression evaluation confirmed up‐regulation of integrin α2β1 as well as the osteogenic genes BGLAP, COL1A1, and RUNX2. Following use of integrin α2β1 blocker antibody, the protein level of integrin α2β1 in cells seeded on PLLA/nHa/Gel scaffolds was decreased compared to control, which confirmed that most of the integrin receptors were bound to gelatin molecules on scaffolds and could activate the integrin α2β1/ERK axis. Collectively, PLLA/nHa/Gel scaffold is a suitable platform for hBM‐MSCs adhesion, proliferation, and osteogenic differentiation in less time via activating integrin α2β1/ERK axis, and thus it might be applicable in bone tissue engineering.

中文翻译：

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通过增强整合素α2β1的表达，提高人间充质干细胞在改性的PLLA纳米纤维上的生物矿化功效，修饰的PLLA纳米纤维涂覆有生物活性材料

当前对骨缺损的治疗性干预主要集中在寻找通过激活相关的细胞内信号传导途径来诱导骨再生的最佳生物活性材料。整联蛋白是跨膜受体，可促进细胞-细胞外基质（ECM）相互作用并激活信号转导。为了开发合适的平台来支持人骨髓间充质干细胞（hBM-MSC）分化为骨组织，将静电纺丝的聚L-丙交酯（PLLA）纳米纤维支架涂以纳米羟基磷灰石（PLLA / nHa组），明胶纳米颗粒（PLLA） / Gel组）和nHa / Gel纳米颗粒（PLLA / nHa / Gel组）及其对细胞增殖，成骨细胞生物标志物表达和骨分化的影响进行了比较。P  <.05）。与其他相比，在成骨培养基上在PLLA / nHa / Gel支架上培养的hBM-MSC中，碱性磷酸酶的活性也更高。基因表达评估证实了整合素α2β1以及成骨基因BGLAP，COL1A1和RUNX2的上调。使用整合素α2β1阻断剂抗体后，接种在PLLA / nHa / Gel支架上的细胞中整合素α2β1的蛋白水平与对照相比降低，这证实了大多数整合素受体都与支架上的明胶分子结合，并可以激活整合素α2β1/ ERK轴。总的来说，PLLA / nHa / Gel支架是通过激活整联蛋白α2β1/ ERK轴在更短时间内实现hBM-MSC粘附，增殖和成骨分化的合适平台，因此可能适用于骨组织工程。