Department of Periodontology, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, China.
State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong 250013, China.
Acta Biomater. 2020 Jan 1;101:554-564. doi: 10.1016/j.actbio.2019.10.044. Epub 2019 Nov 2.
Nanostructured hydroxyapatite (HAp) has been applied widely as a scaffold material for bone tissue engineering for its good osteoinduction and biodegradability. However, the degradation process and the distribution of degraded HAp within the bone-defect cavity is still not clear. To visually study the behavior of HAp in bone repair process, a membrane of HAp/terbium (Tb)-HAp nanowires (NWs) was prepared with a concentric circle structure (CCS), of which the inner circle and the outer ring were constructed with Tb-HAp and HAp NWs, respectively. HAp/Tb-HAp CCS membrane possessed good osteogenic capacity and efficient fluorescence in the center for visualization. The in vitro experimental results proved that the Tb-HAp and HAp NWs membranes both presented high cytocompatibility and adequate efficiency to induce osteogenic differentiation of bone marrow stem cells (BMSCs). HAp/Tb-HAp CCS membranes were then implanted into a rat calvarial bone-defect model to study the behavior of HAp in bone repair process in vivo by tracking the fluorescence distribution. The results showed that the fluorescence of Tb-HAp diffused gradually from the inner circle to the outer ring, which suggested that the HAp was first degraded, and then the degraded product was diffused and finally reconstructed. Further, the histological results proved that the doping of Tb did not impair the promotive effect of HAp on bone repair process. Therefore, this study provided a visual method to observe the degradation-diffusion-reconstruction behavior of HAp nanomaterials in bone repair process. STATEMENT OF SIGNIFICANCE: The study of dynamic degradation process of implanted hydroxyapatite (HAp) materials in bone-defect cavity is of great significance to bone tissue engineering applications. Here, we designed a HAp/Tb-HAp nanowires (NWs) membrane with concentric circle structure (CCS) to visibly observe the behavior of HAp during bone repair process. HAp/Tb-HAp CCS membrane possessed both osteoinduction ability and fluorescence property. Calvarial bone-defect repair experiments in vivo showed that the fluorescence of Tb-HAp diffused gradually from inner circle to outer ring, which suggested that HAp was first degraded, then diffused and finally reconstructed. Therefore, this invention provides not only a visible method to observe the degradation-diffusion-reconstruction behavior of HAp-based biomaterials, but also a basic understanding of the dynamic change of HAp-based biomaterials.
纳米结构羟基磷灰石(HAp)因其良好的成骨诱导性和生物降解性而被广泛应用于骨组织工程支架材料。然而,HAp 的降解过程及其在骨缺损腔内的分布仍不清楚。为了直观地研究 HAp 在骨修复过程中的行为,我们制备了一种具有同心圆结构(CCS)的 HAp/Tb-HAp 纳米线(NWs)膜,其中内圈和外圈分别由 Tb-HAp 和 HAp NWs 构建。HAp/Tb-HAp CCS 膜具有良好的成骨能力和中心的高效荧光可视化能力。体外实验结果证明,Tb-HAp 和 HAp NWs 膜均具有高细胞相容性和足够的诱导骨髓间充质干细胞(BMSCs)成骨分化的效率。然后将 HAp/Tb-HAp CCS 膜植入大鼠颅骨骨缺损模型中,通过跟踪荧光分布来研究 HAp 在体内骨修复过程中的行为。结果表明,Tb-HAp 的荧光从内圈逐渐扩散到外圈,这表明 HAp 首先降解,然后降解产物扩散并最终重建。进一步的组织学结果证明,Tb 的掺杂并不损害 HAp 对骨修复过程的促进作用。因此,本研究提供了一种可视化方法来观察 HAp 纳米材料在骨修复过程中的降解-扩散-重建行为。