Studying Mechanotransduction in Late Embryonic Development to Inform Tendon Tissue Engineering
研究胚胎发育晚期的力转导为肌腱组织工程提供信息
基本信息
- 批准号:9808374
- 负责人:
- 金额:$ 18.81万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-07-01 至 2021-06-30
- 项目状态:已结题
- 来源:
- 关键词:AllogenicAreaAutologousAutomobile DrivingBiocompatible MaterialsBiologicalBiological ProductsCRISPR/Cas technologyCell VolumesCellsChick EmbryoChickensCollagen FibrilComputer SimulationCuesDevelopmentDiseaseEmbryoEmbryonic DevelopmentEngineeringEventExperimental ModelsFailureFoundationsFutureGenesHarvestHumanImageImaging TechniquesIn VitroInstructionInvestigationKnock-outKnowledgeLengthLigamentsMechanical StimulationMechanicsMediatingMetatarsal bone structureModulusMorbidity - disease rateMuscleMusculoskeletal DiseasesPTK2 genePainPhasePropertyProtocols documentationQuality of lifeRuptureSignal TransductionSiteSlideStimulusStructureTechniquesTendon InjuriesTendon structureTestingTimeTissue EngineeringTissuesTransplanted tissueUnited StatesWeight-Bearing stateWorkbasecell behaviordesigndisabilitydisease transmissiondisorder riskextracellularfallshatchingimprovedin vivoinjuredinnovationknockout geneligament injurymechanical drivemechanical loadmechanical propertiesmechanotransductionnovelpreventrepairedresponsescaffoldself assemblyself organizationtendon developmenttissue culture
项目摘要
Project Summary/Abstract
Tendon and ligament injuries are a common cause of disability and pain. In many cases, the injured tissue cannot
be repaired directly and must be replaced with a graft material. Ideally, a tissue engineered biomaterial could be
used for this purpose; however, no tissue engineered construct has been successfully used to reconstruct human
tendon or ligament ruptures. A primary reason for the failure in producing successful tendon replacements is that
most tissue engineering approaches do not replicate normal tendon development. Scaffold-free techniques
based on cellular self-assembly are able to generate tissues that that match the structure and mechanics of early
embryonic tendon. However, they are unable to undergo a critical phase in late tendon development where the
collagen fibrils elongate and fuse together generating a substantially stiffer and stronger material. One reason
for this is that the constructs lacked the mechanical stimulation normally provided in vivo by muscles. In fact,
chick embryo muscle activity peaks during late tendon development and this muscle activity is responsible for
increasing the modulus of embryonic tendons. Nevertheless, while mechanical loading of constructs does
improve tissue mechanics, they still fail to match the order-of-magnitude increase in mechanical properties
observed in embryonic chick tendons. A critical barrier is the lack of knowledge regarding the
mechanotransduction mechanisms that determine the cellular response to mechanical stimulation and drive late
tendon development. Understanding how tendon cells respond to mechanical stimuli due to not only muscle
loading but also the local changes in tissue structure and mechanics that occur during development is necessary
to develop biomaterials that can successfully replicate tendon function. Therefore, the objective of this project is
to identify the mechanotransduction mechanisms that mediate the multiscale changes in tissue structure and
mechanics observed during late tendon development. Specifically, this project will (1) identify the multiscale
structural and mechanical changes that occur during late tendon development and (2) determine the
mechanotransduction mechanisms driving these changes. The overall hypothesis is that cells sense mechanical
stimuli through a combination of cell-cell and cell-matrix interactions and that these mechanotransduction events
are essential for driving proper tendon development. This will be evaluated by inhibiting embryonic muscle
activity and perturbing mechanotransduction signaling in embryonic tendons via site-specific gene knockout
during ex ovo culture of chicken embryos. The effects of these manipulations on tendon structure and mechanics
will be determined by a novel combination of multiscale mechanical testing, computational modeling, and
ultrastructural imaging. This work is the first investigation of the mechanotransduction mechanisms driving the
structural and mechanical changes observed during late tendon development. The findings will provide the
foundation for enhancing tissue engineered constructs to develop biomaterials that can successfully replace
diseased tendons and ligaments.
项目总结/摘要
肌腱和韧带损伤是残疾和疼痛的常见原因。在许多情况下,受伤的组织不能
直接修复,必须用移植材料替换。理想情况下,组织工程生物材料可以
用于此目的;然而,没有组织工程构建体已成功地用于重建人类,
肌腱或韧带断裂。肌腱置换失败的主要原因是,
大多数组织工程方法不能复制正常的肌腱发育。无支架技术
基于细胞自组装的细胞能够产生与早期细胞的结构和力学相匹配的组织。
胚胎腱然而,它们不能经历肌腱发育后期的关键阶段,
胶原原纤维伸长并融合在一起,产生基本上更硬和更强的材料。一个原因
这是因为该结构缺乏通常由肌肉在体内提供的机械刺激。事实上,
鸡胚肌肉活动在肌腱发育后期达到峰值,这种肌肉活动负责
增加胚胎肌腱的模量。尽管如此,尽管结构的机械载荷
尽管改善了组织力学,但它们仍然无法匹配机械性能的数量级增加,
在鸡胚肌腱中观察到。一个关键的障碍是缺乏关于
机械转导机制决定细胞对机械刺激的反应,
肌腱发育了解肌腱细胞如何对机械刺激做出反应,不仅因为肌肉
但是在发育过程中发生的组织结构和力学的局部变化也是必要的
开发出可以成功复制肌腱功能的生物材料。因此,本项目的目标是
确定介导组织结构多尺度变化的机械传导机制,
在后期肌腱发育过程中观察到的力学。具体而言,该项目将(1)确定多尺度
结构和力学变化发生在后期肌腱发育和(2)决定
驱动这些变化的机械转导机制。总的假设是,细胞感觉机械
通过细胞-细胞和细胞-基质相互作用的组合刺激,并且这些机械转导事件
是驱动肌腱正常发育的关键这将通过抑制胚胎肌肉来评估
通过位点特异性基因敲除激活和干扰胚胎肌腱中的机械传导信号
在鸡胚的卵外培养期间。这些手法对肌腱结构和力学的影响
将通过多尺度力学测试、计算建模和
超微结构成像这项工作是第一次调查的机械转导机制驱动的
结构和机械变化观察后期肌腱发展。调查结果将提供
增强组织工程结构的基础,以开发可成功替代
病变的肌腱和韧带
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Spencer Szczesny其他文献
Spencer Szczesny的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Spencer Szczesny', 18)}}的其他基金
Colocalization of gene expression and microscale tissue strains in live tendon explants using barcoded biosensors
使用条形码生物传感器对活体肌腱外植体中的基因表达和微型组织菌株进行共定位
- 批准号:
10558584 - 财政年份:2022
- 资助金额:
$ 18.81万 - 项目类别:
Colocalization of gene expression and microscale tissue strains in live tendon explants using barcoded biosensors
使用条形码生物传感器对活体肌腱外植体中的基因表达和微型组织菌株进行共定位
- 批准号:
10373315 - 财政年份:2022
- 资助金额:
$ 18.81万 - 项目类别:
Role of Mechanical Loading and Stem Cell Mechanotransduction in Tendon Degeneration
机械负荷和干细胞力转导在肌腱退变中的作用
- 批准号:
9320001 - 财政年份:2016
- 资助金额:
$ 18.81万 - 项目类别:
相似国自然基金
层出镰刀菌氮代谢调控因子AreA 介导伏马菌素 FB1 生物合成的作用机理
- 批准号:2021JJ40433
- 批准年份:2021
- 资助金额:0.0 万元
- 项目类别:省市级项目
寄主诱导梢腐病菌AreA和CYP51基因沉默增强甘蔗抗病性机制解析
- 批准号:32001603
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
AREA国际经济模型的移植.改进和应用
- 批准号:18870435
- 批准年份:1988
- 资助金额:2.0 万元
- 项目类别:面上项目
相似海外基金
Onboarding Rural Area Mathematics and Physical Science Scholars
农村地区数学和物理科学学者的入职
- 批准号:
2322614 - 财政年份:2024
- 资助金额:
$ 18.81万 - 项目类别:
Standard Grant
TRACK-UK: Synthesized Census and Small Area Statistics for Transport and Energy
TRACK-UK:交通和能源综合人口普查和小区域统计
- 批准号:
ES/Z50290X/1 - 财政年份:2024
- 资助金额:
$ 18.81万 - 项目类别:
Research Grant
Wide-area low-cost sustainable ocean temperature and velocity structure extraction using distributed fibre optic sensing within legacy seafloor cables
使用传统海底电缆中的分布式光纤传感进行广域低成本可持续海洋温度和速度结构提取
- 批准号:
NE/Y003365/1 - 财政年份:2024
- 资助金额:
$ 18.81万 - 项目类别:
Research Grant
Point-scanning confocal with area detector
点扫描共焦与区域检测器
- 批准号:
534092360 - 财政年份:2024
- 资助金额:
$ 18.81万 - 项目类别:
Major Research Instrumentation
Collaborative Research: Scalable Manufacturing of Large-Area Thin Films of Metal-Organic Frameworks for Separations Applications
合作研究:用于分离应用的大面积金属有机框架薄膜的可扩展制造
- 批准号:
2326714 - 财政年份:2024
- 资助金额:
$ 18.81万 - 项目类别:
Standard Grant
Collaborative Research: Scalable Manufacturing of Large-Area Thin Films of Metal-Organic Frameworks for Separations Applications
合作研究:用于分离应用的大面积金属有机框架薄膜的可扩展制造
- 批准号:
2326713 - 财政年份:2024
- 资助金额:
$ 18.81万 - 项目类别:
Standard Grant
Unlicensed Low-Power Wide Area Networks for Location-based Services
用于基于位置的服务的免许可低功耗广域网
- 批准号:
24K20765 - 财政年份:2024
- 资助金额:
$ 18.81万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
RAPID: Collaborative Research: Multifaceted Data Collection on the Aftermath of the March 26, 2024 Francis Scott Key Bridge Collapse in the DC-Maryland-Virginia Area
RAPID:协作研究:2024 年 3 月 26 日 DC-马里兰-弗吉尼亚地区 Francis Scott Key 大桥倒塌事故后果的多方面数据收集
- 批准号:
2427233 - 财政年份:2024
- 资助金额:
$ 18.81万 - 项目类别:
Standard Grant
Postdoctoral Fellowship: OPP-PRF: Tracking Long-Term Changes in Lake Area across the Arctic
博士后奖学金:OPP-PRF:追踪北极地区湖泊面积的长期变化
- 批准号:
2317873 - 财政年份:2024
- 资助金额:
$ 18.81万 - 项目类别:
Standard Grant
RAPID: Collaborative Research: Multifaceted Data Collection on the Aftermath of the March 26, 2024 Francis Scott Key Bridge Collapse in the DC-Maryland-Virginia Area
RAPID:协作研究:2024 年 3 月 26 日 DC-马里兰-弗吉尼亚地区 Francis Scott Key 大桥倒塌事故后果的多方面数据收集
- 批准号:
2427232 - 财政年份:2024
- 资助金额:
$ 18.81万 - 项目类别:
Standard Grant