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新型自收缩植骨胶带协同调控YAP促进牙槽突裂微应力感应成骨的应用及机制研究

批准号:
82101076
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
朱舟
依托单位:
学科分类:
口腔颅颌面组织生物力学和生物材料
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
朱舟

项目摘要

结项摘要

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中文摘要
牙槽突裂是常见的先天颌面部缺损疾病。现阶段的牙槽突裂植骨术面临着患儿创口完善关闭困难、移植骨与缺损部位难以紧密结合、缺损区原位成骨活性不足的挑战,导致植骨区域骨创封闭不佳、成骨感应迟钝、成骨动力缺乏。针对牙槽突裂植骨术的临床难题,本项目拟制备一种自收缩生物胶带用于牙槽突裂植骨术,利用胶带中的儿茶酚基团实现术区的粘接封闭;以热感自收缩电纺纤维持续释放微应力激活成骨感应;同时依靠复合微球材料内源性构建富镁环境,进一步放大成骨动力,协同上调YAP促进植骨术区微应力感应成骨。本项目拟筛选制备参数优化胶带性能;以体内外牙槽突裂植骨模拟实验探究材料的成骨效应;通过表征YAP、ITG和GSN等节点蛋白的表达水平,察明材料在基因层面对应力感应成骨的协同激活作用,并探究其成骨传导机制。期望该胶带能突破牙槽突裂植骨术的临床瓶颈,保障牙槽突裂的骨修复效果。
英文摘要
Alveolar cleft is a common congenital maxillofacial defect disease. The current bone grafting for alveolar cleft is obstructed with the difficulty of wound’s complete closure, slack combining between the graft and the defect bone, insufficient in-situ osteogenic activity of the cleft area, resulting in poor closure, weak osteogenesis -induction and osteogenesis motion. Aiming at the clinical problems of alveolar cleft bone grafting, this project intends to prepare a self-shrinking biotape for alveolar, using the catechol modified tape to realize the bonding and sealing of the operation alveolar; Thermal shrinkage electrospun fibers continue to auto-shrink to activate osteogenic induction; at the same time, relying on the composite microsphere building an Mg2+-rich environment endogenously, thus further amplifies the osteogenesis dynamics, all the components synergistically increases YAP to promote micro-stress-induced osteogenesis in the bone grafting area. This project intends to screen the component parameters to optimize the physical and chemical properties of the tape; through in vivo and in vitro alveolar cleft bone grafting simulation experiments, explore the osteogenic effect of the material; using the characterization of node proteins such as YAP, ITG and GSN to verified the mechanism which the noval tape using to synergistically promote osteogenesis and explore its osteogenic conduction pathway. It is expected that the tape could break through the clinical bottleneck of alveolar cleft bone grafting and ensure its bone repair effect.
植骨术是现阶段应对牙槽骨量不足的主要治疗方案。然而,当牙槽突裂等骨缺损患者尚未成年时,由于骨生长发育变化的特性,仍存在骨创封闭不佳、成骨感应迟钝、成骨动力缺乏等挑战。据此,本项目依据研究团队长期在组织工程水凝胶材料材料领域的积累,聚焦牙槽骨力学生理和矿化生理的多方面进行协同调控,设计研发了兼具生理屏障、生理应力、生理矿化的复层水凝胶骨胶带PN-GEL@BP-PE。该水凝胶以低温逐层组装及3D打印制备,集成骨粘附、微应力供给和矿化环境诱导功能。研究显示,PN-GEL@BP-PE表现出优异的骨粘接性能,并可自主响应体温向其所粘接的骨端施加微应力,构建促成骨应力微环境;同时,水凝胶负载的纳米黑磷将主动募集钙离子,构建骨再生矿化微环境。分子生物学研究表明,PN-GEL@BP-PE打造的应力微环境将激活骨干细胞内YAP,促进β-catenin核内移,结合矿化微环活,协同上调RUNX2等关键成骨靶点的表达促进骨再生。体内研究中,PN-GEL@BP-PE的应用显著加快了骨缺损的愈合速度,并增强了新生骨的质量和密度。综上,本项目通过PN-GEL@BP-PE复层水凝胶骨胶带,打造的骨屏障保护、骨微应力激活和骨矿化微环境的协同策略,可顺应骨再生的生理需求,并为生物水凝胶用于骨组织工程的设计和临床应用提供了灵感和理论实验基础。
基于仿生活体腺泡模型探究微应力调控唾液腺损伤及修复的应用基础研究
  • 批准号:
    82371012
  • 项目类别:
    面上项目
  • 资助金额:
    47万元
  • 批准年份:
    2023
  • 负责人:
    朱舟
  • 依托单位:
国内基金
海外基金