The use of cell‐free scaffolds containing bioactive molecules having a controlled released pattern has been proposed as a promising approach in field of tissue engineering. This system would eliminate the challenges associated with cell implantation. For bone tissue engineering, in particular, the environment in favor of both de novo bone formation and vascularization are considered critical approach. Erythropoietin (EPO) has been shown to have bone‐related pleiotropic effects. However, due to the adverse systemic side effect, its local administration with controlled release has been recommended. This study aimed to fabricate erythropoietin (EPO)‐releasing poly lactic acid (PLA)/nanoclay (NC)/nanohydroxyaptitite (nHA) as a new scaffold for bone tissue engineering application. PLA/NC/nHA‐EPO scaffolds were fabricated using thermally induced phase separation technique. The fabricated scaffolds were first characterized in terms of morphology and physical properties, as well as their EPO realizing pattern. Then, their biocompatibility was assessed in response to the MG‐63 human osteoblast‐like cell line. Finally, its bone regeneration capability was evaluated in a rat calvarial model. The result showed that the fabricated scaffolds presented acceptable physical properties with the sustained release of EPO. The in vitro biocompatibility was also approved. Their bone regeneration in rat calvaria showed that the PLA/NC/nHA‐EPO scaffolds were significantly able to generate bone formation (41% after 8 weeks). Also, the formation of new vessels and capillaries were evident. The presence of osteoblast in the defect also confirmed that the EPO was potent in inducing mesenchymal stem cells chemotaxis. The PLA/NC/nHA containing EPO could be a promising cell‐free bioscaffold for bone tissue regeneration.

中文翻译：

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通过热诱导相分离技术制备的含有促红细胞生成素的羟基磷灰石纳米载体的无细胞聚乳酸/纳米粘土支架的研究，用于骨组织工程应用

已提出使用含有具有受控释放模式的生物活性分子的无细胞支架作为组织工程领域中的一种有前途的方法。该系统将消除与细胞植入相关的挑战。特别是对于骨组织工程，有利于从头进行骨形成和血管形成的环境被认为是关键方法。促红细胞生成素（EPO）已显示具有骨骼相关的多效性作用。然而，由于不利的全身性副作用，建议局部控制给药。这项研究旨在制造释放促红细胞生成素（EPO）的聚乳酸（PLA）/纳米粘土（NC）/纳米羟基磷灰石（nHA）作为骨组织工程应用的新型支架。PLA / NC / nHA-EPO支架是使用热诱导相分离技术制造的。首先根据形态和物理性质以及它们的EPO实现模式来表征所制造的支架。然后，评估它们对MG-63人成骨细胞样细胞系的反应的生物相容性。最后，在大鼠颅骨模型中评估了其骨再生能力。结果表明，所制备的支架具有持续释放EPO的可接受的物理性能。体外生物相容性也被批准。它们在大鼠颅骨中的骨再生表明，PLA / NC / nHA-EPO支架能够显着生成骨形成（8周后占41％）。同样，新血管和毛细血管的形成也很明显。缺损中成骨细胞的存在也证实了EPO在诱导间充质干细胞趋化性方面很有效。含EPO的PLA / NC / nHA可能是一种有希望的无骨生物支架，可用于骨组织再生。