Safarova Yantsen Yuliya, Nessipbekova Assem, Syzdykova Aizhan, Olzhayev Farkhad, Umbayev Bauyrzhan, Kassenova Aliya, Fadeeva Inna V, Askarova Sholpan, Rau Julietta V
National Laboratory Astana, Nazarbayev University, Kabanbay batyr Ave. 53, 010000 Astana, Kazakhstan.
A. A. Baikov Institute of Metallurgy and Material Science RAS, Leninskie, 49, 119334 Moscow, Russia.
J Funct Biomater. 2024 Nov 20;15(11):352. doi: 10.3390/jfb15110352.
Pathological bone fracturing is an escalating problem driven by increasing aging and obesity. Bioceramics, particularly tricalcium-phosphate-based materials (TCP), are renowned for their exceptional biocompatibility, osteoconductivity, and ability to promote biomineralization. In the present study, we designed and characterized TCP porous granules doped with strontium (Sr) and copper (Cu) (CuSr TCP). Sr ions were selected as Sr plays a crucial role in early bone formation, osteogenesis, and angiogenesis; Cu ions possess antibacterial properties.
The synthesized CuSr TCP granules were characterized by X-ray diffraction. Cytotoxicity and cell proliferation analyses' assays were performed through the lactate dehydrogenase (LDH) activity and CCK-8 viability tests in rat bone marrow-derived mesenchymal stem cells (BM-MSCs). Hemolytic activity was carried out with human red blood cells (RBCs). Early and late osteogenesis were assessed with alkaline phosphatase (ALP) and Alizarin Red S activity in human osteoblast progenitor cells and rat BM-MSCs. The influence of CuSr TCP on angiogenesis was investigated in human umbilical vein endothelial cells (HUVECs).
We have demonstrated that media enriched with CuSr TCP in concentrations ranging from 0.1 mg/mL to 1 mg/mL were not cytotoxic and did not significantly affect cell proliferation rate motility. Moreover, a concentration of 0.5 mg/mL showed a 2.5-fold increase in the migration potential of BM-MSCs. We also found that CuSr TCP-enriched media slightly increased early osteogenesis. We also found that Sr and Cu substitutions in TCP particles significantly enhanced the measured angiogenic parameters compared to control and unsubstituted TCP granules.
Our results demonstrate that TCP porous granules doped with Sr and Cu are biocompatible, promote osteodifferentiation and angiogenesis, and could be recommended for further in vivo studies.
随着老龄化加剧和肥胖率上升，病理性骨折问题日益严重。生物陶瓷，尤其是磷酸三钙基材料（TCP），因其卓越的生物相容性、骨传导性和促进生物矿化的能力而闻名。在本研究中，我们设计并表征了掺杂锶（Sr）和铜（Cu）的TCP多孔颗粒（CuSr TCP）。选择Sr离子是因为Sr在早期骨形成、骨生成和血管生成中起关键作用；Cu离子具有抗菌特性。
通过X射线衍射对合成的CuSr TCP颗粒进行表征。通过乳酸脱氢酶（LDH）活性和CCK - 8活力测试，在大鼠骨髓间充质干细胞（BM - MSCs）中进行细胞毒性和细胞增殖分析。用人红细胞（RBCs）进行溶血活性检测。在人成骨细胞祖细胞和大鼠BM - MSCs中，通过碱性磷酸酶（ALP）和茜素红S活性评估早期和晚期骨生成。在人脐静脉内皮细胞（HUVECs）中研究CuSr TCP对血管生成的影响。
我们已经证明，浓度范围为0.1 mg/mL至1 mg/mL的富含CuSr TCP的培养基无细胞毒性，且对细胞增殖率和运动性无显著影响。此外，0.5 mg/mL的浓度使BM - MSCs的迁移潜能提高了2.5倍。我们还发现富含CuSr TCP的培养基略微增加了早期骨生成。我们还发现，与对照和未取代的TCP颗粒相比，TCP颗粒中的Sr和Cu取代显著提高了测量的血管生成参数。
我们的结果表明，掺杂Sr和Cu的TCP多孔颗粒具有生物相容性，促进骨分化和血管生成，可推荐用于进一步的体内研究。
