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脱细胞脂肪组织基质涂覆和辛伐他汀负载的羟基磷灰石微球用于骨再生。

Decellularized adipose tissue matrix-coated and simvastatin-loaded hydroxyapatite microspheres for bone regeneration.

机构信息

Department of Biotechnology, Middle East Technical University, Ankara, Turkey.

Department of Metallurgical and Materials Engineering, Middle East Technical University, Ankara, Turkey.

出版信息

Biotechnol Bioeng. 2022 Sep;119(9):2574-2589. doi: 10.1002/bit.28154. Epub 2022 Jun 23.

Abstract

Simvastatin (SIM)-loaded and human decellularized adipose tissue (DAT)-coated porous hydroxyapatite (HAp) microspheres were developed for the first time to investigate their potential on bone regeneration. Microspheres were loaded with SIM and then coated with DAT for modifying SIM release and improving their biological response. HAp microspheres were prepared by water-in-oil emulsion method using camphene (C H ) as porogen followed by camphene removal by freeze-drying and sintering at 1200°C for 3 h. Sintered HAp microspheres with an average particle size of ~400 µm were porous and spherical in shape. Microspheres were incubated with 1, 2.5, and 5 mg/ml SIM stock solutions for drug loading, and drug loading was determined as 7.5 ± 0.79, 20.41 ± 1.93, and 46.26 ± 0.29 µg SIM/mg microspheres, respectively. SIM loading increased with the increase of the initial SIM loading amount. Faster SIM release was observed in DAT-coated microspheres compared to bare counterparts. Higher SaoS-2 cell attachment and proliferation were observed on DAT-coated microspheres. Significantly higher alkaline phosphatase activity of SaoS-2 cells was observed on DAT-coated microspheres containing 0.01 mg/ml SIM than all other groups (p < 0.01). DAT-coated microspheres loaded with SIM at low doses hold promise for bone tissue engineering applications.

摘要

辛伐他汀(SIM)负载和人去细胞脂肪组织(DAT)涂层多孔羟基磷灰石(HAp)微球首次被开发用于研究其在骨再生中的潜力。微球被加载 SIM,然后用 DAT 涂层以修饰 SIM 释放并改善其生物学反应。HAp 微球通过使用莰烯(C H )作为致孔剂的油包水乳液方法制备,然后通过冷冻干燥除去莰烯,并在 1200°C 下烧结 3 小时。烧结的 HAp 微球具有平均粒径约为 400µm,呈多孔和球形。微球用 1、2.5 和 5mg/ml SIM 储备溶液孵育进行药物负载,药物负载分别确定为 7.5±0.79、20.41±1.93 和 46.26±0.29µg SIM/mg 微球。SIM 负载随初始 SIM 负载量的增加而增加。与裸微球相比,DAT 涂层微球中观察到更快的 SIM 释放。在 DAT 涂层微球上观察到更高的 SaoS-2 细胞附着和增殖。在含 0.01mg/ml SIM 的 DAT 涂层微球上观察到 SaoS-2 细胞的碱性磷酸酶活性明显高于所有其他组(p<0.01)。负载低剂量 SIM 的 DAT 涂层微球有望用于骨组织工程应用。

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