组胺素1促进干细胞在3D打印支架材料表面粘附效果及其信号转导机制研究

批准号:
31800808
项目类别:
青年科学基金项目
资助金额:
20.0 万元
负责人:
王冬赟
依托单位:
学科分类:
C1003.组织工程学
结题年份:
2021
批准年份:
2018
项目状态:
已结题
项目参与者:
Enno . C . I . Veerman、裴涛、刘开蕾、林云涛、李博文、孙帅
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中文摘要
以个性化、结构可控的3D打印支架为基础的骨组织工程技术是大体积骨缺损修复领域新的研究热点。而细胞在材料表面粘附是这一技术的成功关键之一。课题组研究证实:人唾液来源的组胺素(Hst1)及其衍生物可高效促进上皮、内皮细胞在多种材料表面粘附、铺展和迁移。与表面修饰方式相比,Hst1可与细胞直接混合,高效快速促进细胞粘附,因而对不同打印材料具有广泛适用性。课题组预实验显示:Hst1在低活性表面也能显著促进成骨前体细胞铺展。然而Hst1促进间充质干细胞(MSCs)在3D打印支架表面粘附、铺展、迁移效果及其信号机制尚未明确。本项目中,课题组将1)体外、体内检测干细胞在3D打印支架上粘附、迁移及存活率,筛选出最优Hst1剂量;2)利用通路蛋白芯片、western等分子生物学手段,揭示 Hst1作用机制;3)体内验证Hst1/MSC-3D打印支架修复大体积骨缺损效果。为其临床应用提供理论依据和实验基础。
英文摘要
The customized 3D-priting-based bone tissue engineering is one of the hottest research focus in the field of the repair of large bone defects. The attachment of cells on the scaffold surface is one of the key factors for successful bone regeneration. Our preliminary research has proved that histantin-1(Hst1) and its deviations can effectively improve the attachment, spreading and migration of epithelial and endothelial cells on various scaffold materials. Compare to other techniques for surface modification, Hst1 can be mixed with cells directly and enhance cell attachment with high efficiency. Our pilot study showed that Hst1 can improve the spreading of pre-osteoblasts even on surfaces with low activity. However, it is still not clear that the effect of Hst1 on improving the attachment, spreading and migration of mesenchymal stem cells on 3D-printing scaffold. The aim of this project is to construct a histantin-1(Hst1)-modified 3D-priting scaffold to repair large bone defect, to evaluate its efficacy for bone regeneration and to explore the signaling pathway and molecular mechanism. Firstly, we will test the effect of Hst1 on the adhesion of mesenchymal stem cell on scaffolds in vitro, so as to optimize the Hst1 dosage on per unit scaffolds; and evaluate the efficacy of repairing large bone defect in vivo. Secondly, we will assess the influence of Hst1-modified 3D-priting scaffold on the loading efficiency of stem cells in vitro and success rate and migration of stem cells in vivo. Thirdly, we will explore the signal pathway and molecular mechanism of how Hst1 regulate the adhesion of stem cells on scaffolds. This project will provide a new strategy for improving the adhesion of mesenchymal stem cells-3D-priting scaffold in bone tissue engineering, and make great benefits for its clinical transformation.
间充质干细胞和基于3D打印的骨组织工程是修复大体积骨缺损的一种有前途的技术。它的成功高度依赖于细胞附着、扩散、成骨分化和干细胞在3D打印支架上的体内存活。在本研究中,我们采用了人唾液组织抑素-1(Hst1)作为细胞靶向策略,以增强3D打印的β-磷酸三钙(β-TCP)支架上人脂肪源性干细胞(HASC)的相互作用。荧光图像显示Hst1显著增加了生物惰性玻璃和3D打印β-TCP支架上HASC的总数和表面积。此外,在3D打印的β-TCP支架上,Hst1与显著高于对照组的增殖、碱性磷酸染色相关。随后,小动物成像显示Hst1处理的hASC/3D打印TCP结构的荧光密度始终显著高于对照组。ERK和p38的特异性抑制剂而非JNK信号显著抑制HASC的粘附。Hst1提高了每个细胞中talin、vinculin和paxilin的总荧光强度。综上所述,Hst1可显著促进HASC在3D打印β-TCP支架上的粘附、扩散、成骨分化和体内存活,在干细胞/3D打印骨组织工程中具有良好的应用前景。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1111/jcmm.17054
发表时间:2021-12
期刊:Journal of cellular and molecular medicine
影响因子:5.3
作者:Li X;Lin H;Zhang X;Jaspers RT;Yu Q;Ji Y;Forouzanfar T;Wang D;Huang S;Wu G
通讯作者:Wu G
DOI:--
发表时间:2019
期刊:中国口腔种植学杂志
影响因子:--
作者:王冬赟;罗媛;彭娟红
通讯作者:彭娟红
A dual functional bone-defect-filling material with sequential antibacterial and osteoinductive properties for infected bone defect repair
一种具有连续抗菌和骨诱导特性的双功能骨缺损填充材料,用于修复感染骨缺损
DOI:10.1002/jbm.a.36744
发表时间:2019-10-01
期刊:JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
影响因子:4.9
作者:Wang, Dongyun;Liu, Yi;Wu, Gang
通讯作者:Wu, Gang
DOI:https://doi.org/10.1111/ jcmm.17054
发表时间:2021
期刊:J Cell Mol Med
影响因子:--
作者:Xumin Li;Haiyan Lin;Xiaorong Zhang;Richard T. Jaspers;Qihao Yu;Yinghui Ji;Tim Forouzanfar;Dongyun Wang;Shengbin Huang;Gang Wu
通讯作者:Gang Wu
国内基金
海外基金
