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负载冻干浓缩生长因子的3D打印仿生骨支架通过调节VEGFR2/PI3K/AKT信号通路促进骨缺损修复。

3D-printed biomimetic bone scaffold loaded with lyophilized concentrated growth factors promotes bone defect repair by regulation the VEGFR2/PI3K/AKT signaling pathway.

作者信息

Liu Xiuyu, Zhou Jing, Chen Meiqing, Chen Siyu, You Jiaqian, Li Yangyang, Lv Huixin, Zhang Yidi, Zhou Yanmin

机构信息

Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun 130021, China; Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun 130021, China.

Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun 130021, China; Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun 130021, China.

出版信息

Int J Biol Macromol. 2024 Dec;282(Pt 2):136938. doi: 10.1016/j.ijbiomac.2024.136938. Epub 2024 Oct 26.

DOI:10.1016/j.ijbiomac.2024.136938
PMID:39490882
Abstract

This study investigates the effects of concentrated growth factors (CGF) and bone substitutes on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs), as well as the development of a novel 3D-printed biomimetic bone scaffold. Based on the structure of cancellous bone, 3D-printed bionic bone with sustainable release of growth factors and Ca was prepared. Using BMSCs and EA.hy926 in co-culture with the bionic bone scaffold, experimental results demonstrate that this bionic structural design enhances cell proliferation and adhesion, and that the bionic bone possesses the ability to promote bone and vascular regeneration directly. Transcriptomics, western blot analysis, and flow cytometry are employed to investigate the effects of CGF and Ca on the signaling pathways of BMSCs. The study reports that vascular endothelial growth factor (VEGF) released by CGF activated VEGFR2 on BMSCs, leading to Ca influx and activation of the PI3K/AKT signaling pathway, thereby influencing osteogenesis. Animal experiments confirm the ability of the bionic bone to promote osteogenesis in vivo, and its unique degradation pattern accelerates the in vivo repair of bone defects. In conclusion, this study presents a novel biomimetic strategy and, for the first time, explores the potential mechanism by which VEGF and Ca regulate BMSCs differentiation through the VEGFR2/PI3K/AKT signaling pathway. These insights offer a new perspective for the development of innovative bone substitute materials.

摘要

本研究调查了浓缩生长因子(CGF)和骨替代物对骨髓间充质干细胞(BMSCs)增殖和分化的影响,以及一种新型3D打印仿生骨支架的研发情况。基于松质骨结构,制备了具有生长因子和钙持续释放功能的3D打印仿生骨。通过将BMSCs和EA.hy926与仿生骨支架共培养,实验结果表明这种仿生结构设计可增强细胞增殖和黏附,且该仿生骨具有直接促进骨和血管再生的能力。采用转录组学、蛋白质免疫印迹分析和流式细胞术研究CGF和钙对BMSCs信号通路的影响。该研究报告称,CGF释放的血管内皮生长因子(VEGF)激活了BMSCs上的VEGFR2,导致钙内流并激活PI3K/AKT信号通路,从而影响成骨作用。动物实验证实了仿生骨在体内促进成骨的能力,其独特的降解模式加速了骨缺损的体内修复。总之,本研究提出了一种新型仿生策略,并首次探索了VEGF和钙通过VEGFR2/PI3K/AKT信号通路调节BMSCs分化的潜在机制。这些见解为创新骨替代材料的开发提供了新的视角。

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