Coating biopolymer nanofibers with carbon nanotubes accelerates tissue healing and bone regeneration through orchestrated cell- and tissue-regulatory responses
Coating biopolymer nanofibers with carbon nanotubes accelerates tissue healing and bone regeneration through orchestrated cell- and tissue-regulatory responses
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DOI：
10.1016/j.actbio.2020.03.012
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发表时间：
2020-05-01
影响因子：
9.7
通讯作者：
Kim, Hae-Won
中科院分区：
文献类型：
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作者：
Patel, Kapil D.;Kim, Tae-Hyun;Kim, Hae-Won
定制生物材料支架的表面一直是调节有助于组织愈合过程的细胞相互作用的关键策略。特别是，纳米拓扑表面已被证明可以调节干细胞的多种行为，例如初始粘附、扩散和谱系规范。在这里，我们用碳纳米管 (CNT) 定制生物聚合物纳米纤维的表面，以创建独特的双峰纳米级形貌（500 nm 纳米纤维与 25 nm 纳米管），并报告其在调节多种体内反应（包括炎症、血管生成和骨再生）方面的性能。当给予大鼠皮下部位时，碳纳米管涂层的纳米纤维表现出显着减少的炎症症状（下调促炎细胞因子和巨噬细胞聚集）。此外，碳纳米管涂层的纳米纤维显示出显着促进的血管生成反应，增强了新血管形成和血管生成标记物的表达。颅骨骨缺损模型证实了碳纳米管界面所刺激的组织愈合事件。 CNT涂层纳米纤维的体内骨再生显着加速，具有更高的骨矿物质密度和上调体内骨形成细胞的成骨迹象（OPN、OCN、BMP2）。使用 MSC 的体外研究可以证明加速粘附、成骨分化和矿化，支持体内骨形成事件背后的骨促进机制。这些发现强调，生物聚合物纳米纤维的碳纳米管界面在减少炎症、促进血管生成、驱动间充质干细胞的粘附和成骨方面非常有效，最终加速组织愈合和骨再生过程。意义声明在这里，我们证明生物聚合物纳米纤维与碳纳米管（CNT）的界面可以调节细胞和组织的多种相互作用，最终有助于组织愈合和骨再生过程。碳纳米管涂层支架显着减少促炎信号，同时刺激血管生成标记物的表达。此外，碳纳米管涂层支架增加了体内骨形成细胞的骨基质产生，并加速了体外间充质干细胞的粘附和成骨分化。这些集体发现强调，涂覆在生物聚合物纳米纤维上的碳纳米管可以为生物材料表面的纳米级工程创建一个有前景的平台，通过抗炎、促血管生成和干细胞刺激等一系列精心策划的事件，有利于组织愈合和骨再生过程。 (C) 2020 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
Tailoring the surface of biomaterial scaffolds has been a key strategy to modulate the cellular interactions that are helpful for tissue healing process. In particular, nanotopological surfaces have been demonstrated to regulate diverse behaviors of stem cells, such as initial adhesion, spreading and lineage specification. Here, we tailor the surface of biopolymer nanofibers with carbon nanotubes (CNTs) to create a unique bi-modal nanoscale topography (500 nm nanofiber with 25 nm nanotubes) and report the performance in modulating diverse in vivo responses including inflammation, angiogenesis, and bone regeneration. When administered to a rat subcutaneous site, the CNT-coated nanofiber exhibited significantly reduced inflammatory signs (down-regulated pro-inflammatory cytokines and macrophages gathering). Moreover, the CNT-coated nanofibers showed substantially promoted angiogenic responses, with enhanced neoblood vessel formation and angiogenic marker expression. Such stimulated tissue healing events by the CNT interfacing were evidenced in a calvarium bone defect model. The in vivo bone regeneration of the CNT- coated nanofibers was significantly accelerated, with higher bone mineral density and up-regulated osteogenic signs (OPN, OCN, BMP2) of in vivo bone forming cells. The in vitro studies using MSCs could demonstrate accelerated adhesion and osteogenic differentiation and mineralization, supporting the osteo-promoting mechanism behind the in vivo bone forming event. These findings highlight that the CNTs interfacing of biopolymer nanofibers is highly effective in reducing inflammation, promoting angiogenesis, and driving adhesion and osteogenesis of MSCs, which eventually orchestrate to accelerate tissue healing and bone regeneration process.Statement of significanceHere we demonstrate that the interfacing of biopolymer nanofibers with carbon nanotubes (CNTs) could modulate multiple interactions of cells and tissues that are ultimately helpful for the tissue healing and bone regeneration process. The CNT-coated scaffolds significantly reduced the pro-inflammatory signals while stimulating the angiogenic marker expressions. Furthermore, the CNT-coated scaffolds increased the bone matrix production of bone forming cells in vivo as well as accelerated the adhesion and osteogenic differentiation of MSCs in vitro. These collective findings highlight that the CNTs coated on the biopolymer nanofibers allow the creation of a promising platform for nanoscale engineering of biomaterial surface that can favor tissue healing and bone regeneration process, through a series of orchestrated events in anti-inflammation, pro-angiogenesis, and stem cell stimulation. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.