The Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, State Key Laboratory of Bioreactor Engineering, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
ACS Biomater Sci Eng. 2020 Jan 13;6(1):320-328. doi: 10.1021/acsbiomaterials.9b00914. Epub 2019 Dec 6.
The development of biodegradable materials with high osteogenic bioactivity is important for achieving rapid bone regeneration. Although hydroxyapatite (HAp) has been applied as a biomaterial for bone engineering due to its good osteoconductivity, conventional synthetic HAp nanomaterials still lack sufficient osteogenesis, likely due to their high crystallinity and uncontrollable architecture. A design of HAp nanoparticles mimicking bone features may create good microenvironments that promote osteogenesis for rapid bone regeneration. In this study, HAp nanoparticles with a comparatively less crystalline structure and nanorod shapes mimicking biological HAp nanocrystals of natural bone were fabricated using a simple chemical precipitation approach with mild temperature control in the absence of any organic solvents. Transmission electron microscopy (TEM) indicated that HAp nanorods with aspect ratios from 2.0 to 4.4 were synthesized by adjusting the reaction time as well as the reaction temperature. Fourier transform infrared spectroscopy and X-ray diffraction experiments displayed that HAp nanorods prepared at 30 °C (HAp-30 with an aspect ratio of 2.9) had a low crystalline structure and B-type CO substitution similar to those of natural HAp originating from bone tissue. The energy-dispersive spectroscopy (EDS) results showed that the Ca/P ratio of HAp-30 was 1.66 ± 0.13. An in vitro biological evaluation against rat bone marrow-derived mesenchymal stem cells indicated that the resulting HAp nanorods had excellent biocompatibility (with an ∼80-fold increase in IC50 compared to that of conventional HAp nanoparticles). Interestingly, the alkaline phosphatase (ALP), alizarin red S, and immunofluorescence staining results all showed that stem cells display an obvious osteogenesis dependence on the HAp nanostructure. Specifically, HAp nanorods with a moderate aspect ratio had the optimal osteogenic capacity (e.g., HAp-30 offered a 2.8-fold increase in ALP expression and a 4-fold increase in OCN expression relative to that provided by irregular HAp at day 14). It is expected that HAp nanorods with controllable architectures and size have potential as a kind of new bioactive bone filler for bone defect repair.
具有高成骨生物活性的可生物降解材料的开发对于实现快速骨再生至关重要。尽管羟基磷灰石（HAp）由于其良好的骨传导性而被应用于骨工程生物材料，但传统的合成 HAp 纳米材料仍然缺乏足够的成骨能力，这可能是由于其高结晶度和不可控的结构。设计模仿骨特征的 HAp 纳米颗粒可能会创造出促进成骨的良好微环境，从而实现快速骨再生。在这项研究中，使用一种简单的化学沉淀方法，在没有任何有机溶剂的情况下，通过温和的温度控制，制备了具有相对较低结晶结构和纳米棒形状的 HAp 纳米颗粒，模拟天然骨的生物 HAp 纳米晶。透射电子显微镜（TEM）表明，通过调整反应时间和反应温度，可以合成纵横比为 2.0 至 4.4 的 HAp 纳米棒。傅里叶变换红外光谱和 X 射线衍射实验表明，在 30°C 下制备的 HAp 纳米棒（纵横比为 2.9 的 HAp-30）具有低结晶结构和类似于源自骨组织的天然 HAp 的 B 型 CO 取代。能谱（EDS）结果表明，HAp-30 的 Ca/P 比为 1.66±0.13。对大鼠骨髓间充质干细胞的体外生物学评价表明，所得 HAp 纳米棒具有优异的生物相容性（与传统 HAp 纳米颗粒相比，IC50 增加约 80 倍）。有趣的是，碱性磷酸酶（ALP）、茜素红 S 和免疫荧光染色结果均表明，干细胞对 HAp 纳米结构表现出明显的成骨依赖性。具体而言，具有适度纵横比的 HAp 纳米棒具有最佳的成骨能力（例如，HAp-30 在第 14 天提供的 ALP 表达增加了 2.8 倍，OCN 表达增加了 4 倍，而不规则 HAp 提供的表达增加了 2.8 倍）。预计具有可控结构和尺寸的 HAp 纳米棒具有作为一种新型生物活性骨填充剂用于骨缺损修复的潜力。
