Promoting osteoblast proliferation on polymer bone substitutes with bone-like structure by combining hydroxyapatite and bioactive glass
Promoting osteoblast proliferation on polymer bone substitutes with bone-like structure by combining hydroxyapatite and bioactive glass
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羟基磷灰石与生物活性玻璃结合促进类骨结构聚合物骨替代物上成骨细胞增殖
DOI：
10.1016/j.msec.2018.11.006
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Xingrong Song
中科院分区：
文献类型：
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作者：
Baisong Zhao;Haiping Xu;Ying Gao;Jia-Zhuang Xu;Hua-Mo Yin;Ling Xu;Zhong-Ming Li;Xingrong Song
模拟天然骨的结构特征已被证明为由生物惰性聚合物基质和生物活性填料组成的聚合物骨科替代物的机械增强带来显著优势。然而，为了触发有效的骨形成和植入物整合，骨替代物的生物活性起着至关重要的作用。我们假设，与单独使用羟基磷灰石（HA）相比，使用羟基磷灰石（HA）和生物活性玻璃（BG）可以改善聚合物基骨替代物的生物学性能。在此，高密度聚乙烯（PE）复合材料加载HA和BG使用改进的注塑机，可以提供强烈的剪切流动，以调节复合材料的分层结构。形态学观察显示，HA/PE和BG/HA/PE复合材料均形成了高度定向的互锁串状结构。此外，生物活性填料分布均匀。HA和BG的组合促进成骨细胞增殖。其机制是BG上调Runx 2表达（1.51 ± 0.17），激活TAZ/雅普（1.41/0.64）信号通路，促进骨化相关蛋白的产生。BG可通过调控microRNA促进Runx 2 mRNA的表达。Runx 2表达的沉默可以抑制BG诱导的成骨细胞增殖。这些结果表明，具有骨样结构的BG/HA/PE复合材料具有作为骨替代物修复大面积骨缺损的高潜力。
Mimicking the structural features of natural bone has been demonstrated to bring pronounced advantages for mechanical reinforcement of polymeric orthopedic substitutes that are composed of bioinert polymer matrix and bioactive fillers. However, to trigger effective bone formation and implant integration, the bioactivity of bone substitutes plays a vital role. We hypothesized that the use of hydroxyapatite (HA) and bioactive glass (BG), compared to the use of HA alone, could improve the biological properties of polymer-based bone substitutes. Herein, high-density polyethylene (PE) composites loaded with HA and BG were fabricated using a modified injection molding machine that can provide intense shear flow to regulate the hierarchical structure of the composites. Morphological observation revealed that bone-like structures were formed in both HA/PE and BG/HA/PE composites, showing highly oriented interlocked shish kebabs. In addition, the bioactive fillers were distributed uniformly. Osteoblast proliferation was promoted by the combination of HA and BG. The mechanism was the upregulation of Runx2 expression (1.51 ± 0.17) with BG and the activation of the TAZ/YAP (1.41/0.64) signaling pathway, which accelerated the generation of ossification-related proteins. BG can regulate microRNA to promote the mRNA expression of Runx2. The silencing of Runx2 expression can inhibit BG-induced osteoblast proliferation. These results suggest that the BG/HA/PE composites having a bone-like structure have high potential as bone substitutes to repair large bone defects.