{"title":"骨再生相关细胞过程中的掺锶和掺铜陶瓷颗粒","authors":"Yuliya Safarova Yantsen, Assem Nessipbekova, Aizhan Syzdykova, Farkhad Olzhayev, Bauyrzhan Umbayev, Aliya Kassenova, Inna V Fadeeva, Sholpan Askarova, Julietta V Rau","doi":"10.3390/jfb15110352","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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<sup>2+</sup> ions were selected as Sr plays a crucial role in early bone formation, osteogenesis, and angiogenesis; Cu<sup>2+</sup> ions possess antibacterial properties.</p><p><strong>Materials: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"15 11","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11595051/pdf/","citationCount":"0","resultStr":"{\"title\":\"Strontium- and Copper-Doped Ceramic Granules in Bone Regeneration-Associated Cellular Processes.\",\"authors\":\"Yuliya Safarova Yantsen, Assem Nessipbekova, Aizhan Syzdykova, Farkhad Olzhayev, Bauyrzhan Umbayev, Aliya Kassenova, Inna V Fadeeva, Sholpan Askarova, Julietta V Rau\",\"doi\":\"10.3390/jfb15110352\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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<sup>2+</sup> ions were selected as Sr plays a crucial role in early bone formation, osteogenesis, and angiogenesis; Cu<sup>2+</sup> ions possess antibacterial properties.</p><p><strong>Materials: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":15767,\"journal\":{\"name\":\"Journal of Functional Biomaterials\",\"volume\":\"15 11\",\"pages\":\"\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2024-11-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11595051/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Functional Biomaterials\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.3390/jfb15110352\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Functional Biomaterials","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3390/jfb15110352","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
摘要
背景：由于老龄化和肥胖的加剧，病理性骨折问题日益严重。生物陶瓷，尤其是基于磷酸三钙的材料（TCP），以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，我们设计并鉴定了掺杂锶（Sr）和铜（Cu）的 TCP 多孔颗粒（CuSr TCP）。之所以选择 Sr2+ 离子，是因为 Sr 在早期骨形成、成骨和血管生成中起着关键作用；Cu2+ 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。在大鼠骨髓间充质干细胞（BM-MSCs）中通过乳酸脱氢酶（LDH）活性和 CCK-8 细胞活力测试进行细胞毒性和细胞增殖分析。用人红细胞（RBC）进行溶血活性测试。用碱性磷酸酶（ALP）和茜素红 S 活性评估人成骨细胞祖细胞和大鼠骨髓间充质干细胞的早期和晚期成骨情况。在人脐静脉内皮细胞（HUVECs）中研究了 CuSr TCP 对血管生成的影响：结果：我们证明，富含 CuSr TCP 的培养基浓度从 0.1 mg/mL 到 1 mg/mL，均不具有细胞毒性，对细胞增殖率和运动性也没有显著影响。此外，浓度为 0.5 毫克/毫升时，BM-间充质干细胞的迁移潜力增加了 2.5 倍。我们还发现，富含 CuSr TCP 的培养基能轻微增加早期成骨。我们还发现，与对照组和未取代的 TCP 颗粒相比，在 TCP 颗粒中取代 Sr 和 Cu 能显著提高测量的血管生成参数：我们的研究结果表明，掺杂锶和铜的 TCP 多孔颗粒具有生物相容性，可促进骨分化和血管生成，可推荐用于进一步的体内研究。
Strontium- and Copper-Doped Ceramic Granules in Bone Regeneration-Associated Cellular Processes.
Background: 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). Sr2+ ions were selected as Sr plays a crucial role in early bone formation, osteogenesis, and angiogenesis; Cu2+ ions possess antibacterial properties.
Materials: 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).
Results: 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.
Conclusion: 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.
期刊介绍：
Journal of Functional Biomaterials (JFB, ISSN 2079-4983) is an international and interdisciplinary scientific journal that publishes regular research papers (articles), reviews and short communications about applications of materials for biomedical use. JFB covers subjects from chemistry, pharmacy, biology, physics over to engineering. The journal focuses on the preparation, performance and use of functional biomaterials in biomedical devices and their behaviour in physiological environments. Our aim is to encourage scientists to publish their results in as much detail as possible. Therefore, there is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Several topical special issues will be published. Scope: adhesion, adsorption, biocompatibility, biohybrid materials, bio-inert materials, biomaterials, biomedical devices, biomimetic materials, bone repair, cardiovascular devices, ceramics, composite materials, dental implants, dental materials, drug delivery systems, functional biopolymers, glasses, hyper branched polymers, molecularly imprinted polymers (MIPs), nanomedicine, nanoparticles, nanotechnology, natural materials, self-assembly smart materials, stimuli responsive materials, surface modification, tissue devices, tissue engineering, tissue-derived materials, urological devices.
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