2D Covalent Organic Framework Direct Osteogenic Differentiation of Stem Cells.
2D Covalent Organic Framework Direct Osteogenic Differentiation of Stem Cells.
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DOI：
10.1002/adhm.202101737
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发表时间：
2022-05
影响因子：
10
通讯作者：
Gaharwar, Akhilesh K.
中科院分区：
文献类型：
--
作者：
Bhunia, Sukanya;Jaiswal, Manish K.;Singh, Kanwar Abhay;Deo, Kaivalya A.;Gaharwar, Akhilesh K.
二维共价有机骨架是一类新型的结晶多孔有机聚合物，具有广泛的应用前景。然而，差的可加工性、水不稳定性和低水溶性极大地限制了它们的实际生物医学应用。在此，我们报道了一类新的水解稳定的2D COFs，用于持续递送药物以指导干细胞命运。具体地，使用两亲性聚合物Pluronic F127（PLU）稳定基于硼酸盐的COF（COF-5），以产生厚度为约25 nm且直径为约200 nm的COF-PLU纳米颗粒。这些纳米颗粒通过网格蛋白介导的内吞作用内化，并具有高细胞相容性（半抑制浓度~1 mg/mL）。有趣的是，2D COFs诱导人间充质干细胞的成骨分化，这是独一无二的。此外，我们能够在COFs的多孔结构中负载成骨剂地塞米松，以持续递送，进一步增强骨诱导能力。我们的研究结果首次证明，制造水解稳定的2D COFs用于持续递送药物，并证明其骨诱导特性。我们报告了水解稳定的二维（2D）共价有机框架（COFs）的骨诱导能力，以指导干细胞的命运。2D COF的高多孔网络可用于负载治疗剂（地塞米松）以促进矿化基质的形成。
Two–dimensional (2D) covalent organic frameworks (COFs) are emerging class of crystalline porous organic polymer with wide-range of potential applications. However, poor processability, aqueous instability, and low water dispersibility greatly limit their practical biomedical implementation. Herein, we report a new class of hydrolytically-stable 2D COFs for sustained delivery of drug to direct stem cell fate. Specifically, a boronate–based COF (COF-5) is stabilized using amphiphilic polymer Pluronic F127 (PLU) to produce COF-PLU nanoparticle with thickness of ~25 nm, and diameter ~200 nm. These nanoparticles are internalized via clathrin mediated endocytosis and have high cytocompatibility (half inhibitory concentration ~1 mg/mL). Interestingly, the 2D COFs induces osteogenic differentiation in human mesenchymal stem cells, which is unique. In addition, we are able to load osteogenic agent – dexamethasone within the porous structure of COFs for sustain delivery which further enhance the osteoinductive ability. Our results demonstrate for the first time, fabrication of hydrolytically-stable 2D COFs for sustained delivery of drugs and demonstrate its osteoinductive characteristics. We report osteoinductive ability of hydrolytically-stable two-dimensions (2D) covalent organic frameworks (COFs) to direct stem cell fate. The high porous network of 2D COFs can be used to load therapeutics (dexamethasone) to promote formation of mineralized matrix.
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