Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.
BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, Seoul National University, Seoul, 08826, South Korea.
Biomed Eng Online. 2023 Feb 18;22(1):15. doi: 10.1186/s12938-023-01078-y.
Hydroxyapatite (HAp) possesses osteoconductive properties, and its granular form can serve as an effective drug delivery vehicle for bone regeneration. Quercetin (Qct), a plant-derived bioflavonoid, is known to promote bone regeneration; however, its comparative and synergistic effects with the commonly used bone morphogenetic protein-2 (BMP-2) have not been investigated.
We examined the characteristics of newly formed HAp microbeads using an electrostatic spraying method and analyzed the in vitro release pattern and osteogenic potential of ceramic granules containing Qct, BMP-2, and both. In addition, HAp microbeads were transplanted into a rat critical-sized calvarial defect and the osteogenic capacity was assessed in vivo.
The manufactured beads had a microscale size of less than 200 μm, a narrow size distribution, and a rough surface. The alkaline phosphatase (ALP) activity of osteoblast-like cells cultured with the BMP-2-and-Qct-loaded HAp was significantly higher than that of either Qct- or BMP-2-loaded HAp groups. The mRNA levels of osteogenic marker genes such as ALP and runt-related transcription factor 2 were found to be upregulated in the HAp/BMP-2/Qct group compared to the other groups. In micro-computed tomographic analysis, the amount of newly formed bone and bone surface area within the defect was significantly higher in the HAp/BMP-2/Qct group, followed by the HAp/BMP-2 and HAp/Qct groups, which is consistent with the histomorphometrical results.
These results imply that electrostatic spraying can be an efficient strategy to produce homogenous ceramic granules and that the BMP-2-and-Qct-loaded HAp microbeads can serve as effective implants for bone defect healing.
羟磷灰石（HAp）具有骨诱导特性，其颗粒形式可用作骨再生的有效药物输送载体。槲皮素（Qct）是一种植物源性生物类黄酮，已知可促进骨再生；然而，其与常用的骨形态发生蛋白-2（BMP-2）的比较和协同作用尚未得到研究。
我们使用静电喷涂法研究了新形成的 HAp 微珠的特性，并分析了含有 Qct、BMP-2 和两者的陶瓷颗粒的体外释放模式和成骨潜力。此外，将 HAp 微珠移植到大鼠临界尺寸颅骨缺损中，并在体内评估其成骨能力。
所制造的珠粒具有小于 200μm 的微尺度尺寸、较窄的尺寸分布和粗糙的表面。与负载 Qct 的 HAp 或负载 BMP-2 的 HAp 相比，培养有成骨样细胞的 BMP-2 和 Qct 负载的 HAp 的碱性磷酸酶（ALP）活性显著更高。与其他组相比，在 HAp/BMP-2/Qct 组中，成骨标记基因如碱性磷酸酶和 runt 相关转录因子 2 的 mRNA 水平上调。在微计算机断层扫描分析中，与其他组相比，HAp/BMP-2/Qct 组的新形成骨量和缺陷内骨表面积明显更高，其次是 HAp/BMP-2 组和 HAp/Qct 组，这与组织形态计量学结果一致。
这些结果表明，静电喷涂可以是一种生产均匀陶瓷颗粒的有效策略，并且负载 BMP-2 和 Qct 的 HAp 微珠可以用作骨缺损愈合的有效植入物。
