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Enhanced osteogenesis of hydroxyapatite scaffolds by coating with BMP-2-loaded short polylactide nanofiber: a new drug loading method for porous scaffolds

机译:通过负载BMP-2的短聚乳酸纳米纤维涂层增强羟基磷灰石支架的成骨作用:多孔支架的新型载药方法

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摘要

Porous hydroxyapatite (HA) is widely used in porous forms to assist bone defect healing. However, further improvements in biological functions are desired for meeting complex clinical situations such as impaired bone regeneration in poor bone stock. The extracellular matrix (ECM) of human tissues is characterized by nanofibrous structures and a variety of signal molecules. Emulating these characteristics are expected to create a favorable microenvironment for cells and simultaneously allow release of osteogenic molecules. In this study, short polylactide fibers containing BMP-2 were prepared by electrospinning and coated on porous HA scaffolds. The coating did not affect porosity or pore interconnectivity of the scaffold but improved its compressive strength markedly. This fiber coating produced burst BMP-2 release in 1 day followed by a linear release for 24 days. The coating had a significantly lower rat calvarial osteoblasts (RCOBs) adhesion (vs. uncoated scaffold) but allowed normal proliferation subsequently. Bone marrow stem cells (MSCs) on the coated scaffolds expressed a significantly increased alkaline phosphatase activity relative to the uncoated ones. After implantation in canine dorsal muscles, the coated scaffolds formed significantly more new bone at Weeks 4 and 12, and more blood vessels at Week 12. This method offers a new option for drug delivery systems.
机译:多孔羟基磷灰石(HA)以多孔形式广泛用于协助骨缺损的愈合。然而,需要生物学功能的进一步改善来满足复杂的临床情况,例如不良骨质中的骨再生受损。人体组织的细胞外基质(ECM)具有纳米纤维结构和各种信号分子的特征。预期模拟这些特性将为细胞创造良好的微环境,同时释放成骨分子。在这项研究中,通过静电纺丝制备了包含BMP-2的短聚乳酸纤维,并将其涂覆在多孔HA支架上。涂层不影响支架的孔隙率或孔互连性,但是显着提高了其抗压强度。这种纤维涂层在1天之内产生了爆发性的BMP-2释放,随后线性释放了24天。涂层的大鼠颅骨成骨细胞(RCOBs)粘附力明显降低(相对于未涂层的支架),但随后可以正常增殖。与未涂覆的支架相比,涂覆的支架上的骨髓干细胞(MSC)表达出明显增加的碱性磷酸酶活性。植入犬背肌后,涂覆的支架在第4周和第12周形成了更多的新骨骼,在第12周形成了更多的血管。这种方法为药物输送系统提供了新的选择。

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