Engineering Innervated Muscle-Tendon Constructs for Tissue Regeneration
工程神经支配的肌肉肌腱结构用于组织再生
基本信息
- 批准号:7847858
- 负责人:
- 金额:$ 8.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-06-10 至 2011-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAcetylcholineAddressAdultAdvanced DevelopmentAnimalsBiochemicalBiologyBioreactorsCaliberCardiovascular systemCell membraneCharacteristicsCoculture TechniquesCollagenComplexDevelopmentElectric StimulationEngineeringEnvironmentFiberGlycolatesGrowthHindlimbImplantIn VitroInfiltrationInjuryIsometric ExerciseLeadLengthLimb structureLongitudinal StudiesMechanicsMedicineMethodologyMuscleMuscle CellsMuscle ContractionMuscle FibersMusculoskeletalMyosin Heavy ChainsNeonatalNerveNerve Growth FactorsNerve TissueNeuromuscular JunctionNeuronsPhenotypePhysical environmentPlasmidsPolymersProductionProtein IsoformsProteinsRattusRecruitment ActivitySiliconesSimulateSkeletal MuscleSpinal CordStressStructureStudy modelsSystemTailTendon structureTestingTimeTissue EngineeringTissuesTransfectionWorkalpha Bungarotoxinbasedesignend-stage organ failurefetalfunctional restorationimplantationin vitro activityin vivomigrationmuscle engineeringmuscle pharmacologynerve supplyneurotrophic factorrelating to nervous systemresponsesciatic nervethree dimensional structuretissue regeneration
项目摘要
DESCRIPTION (provided by applicant): End-stage organ failure or tissue loss is one of the most devastating and costly problems in medicine. The creation of engineered musculoskeletal tissue with functional myotendinous (MTJ) and neuromuscular (NMJ) junctions will not only restore the function of complex tissues such as muscle, tendon, and nerve following traumatic injury, but can also be used as a model for studying developmental muscle biology and muscle pharmacology. We have demonstrated that the co-culture of fetal nerve tissue with fetal or engineered tendon and engineered muscle tissue produces constructs with viable muscle-tendon interfaces that remain intact during force production, and viable neuromuscular junctions that advance the phenotype of the muscle tissue within the construct [1, 2]. The tissues formed express neonatal structures and do not substantially advance functionally or phenotypically in the absence of electrical or mechanical loading. The purpose of this study is to design, fabricate, and evaluate the structural and contractile characteristics of three-dimensional (3-D) engineered tissues containing myotendinous junctions (MTJ) and neuromuscular junctions (NMJ), two of the principal tissue interfaces required for a functional musculoskeletal construct. We propose to study the long-term viability of these constructs; to increase the expression of neurotrophic proteins like glial derived neurotrophic factor (GDNF) and introduce synthetic, engineered, and tissue based conduits to enhance innervation of the muscle constructs; to use bioreactors to place the nerve-tendon- muscle constructs into physical environments which simulate the stress, strain, and contractile activity resembling the mechanical milieu found in hind limb muscles in vivo; and to implant the constructs in vivo to surround the construct with the actual mechanical and biochemical environment of a hindlimb. Our working hypothesis is that an increase in the number of NMJs in conjunction with applied electrical activity in vitro will lead to a more advanced phenotype in the muscle and tendon, increased force production in the engineered muscles, and stronger and more developed tissue interfaces. In vivo implantation of in vitro engineered constructs will further advance the phenotype and functionality of all tissues and tissue interfaces. This project will address the following specific aims: Specific Aim 1. To design and fabricate nerve-tendon-muscle constructs with functional MTJs and NMJs and evaluate both the structural and functional integrity of the constructs at three time points of development. Specific Aim 2. To develop a conduit system to direct the growth of multiple neural extensions towards the muscle construct thus increasing the innervation ratio of the construct. Specific Aim 3. To evaluate the effect of muscle contraction in response to electrical stimulation on the structure and function of the nerve-tendon-muscle construct. Specific Aim 4. To evaluate the effect of an in vivo implantation into a host animal on the structure and function of the nerve-muscle tendon construct at four weeks.
描述(由申请人提供):终末期器官衰竭或组织损失是医学上最具破坏性和代价最高的问题之一。具有功能性肌腱(MTJ)和神经肌肉(NMJ)连接的工程化肌肉骨骼组织的创建不仅将恢复创伤性损伤后的复杂组织如肌肉、肌腱和神经的功能,而且还可以用作研究发育肌肉生物学和肌肉药理学的模型。我们已经证明,胎儿神经组织与胎儿或工程化肌腱和工程化肌肉组织的共培养产生了具有在力产生期间保持完整的可行肌肉-肌腱界面的构建体,以及促进构建体内肌肉组织表型的可行神经肌肉接头[1,2]。所形成的组织表达新生结构,并且在没有电或机械负载的情况下在功能上或表型上基本上不前进。本研究的目的是设计,制造,并评估三维(3-D)工程组织的结构和收缩特性,包含肌腱接头(MTJ)和神经肌肉接头(NMJ),两个主要的组织界面所需的功能性肌肉骨骼结构。我们建议研究这些结构的长期生存能力;增加神经营养蛋白如胶质源性神经营养因子(GDNF)的表达,并引入合成的、工程化的和基于组织的导管来增强肌肉结构的神经支配;使用生物反应器将神经-肌腱-肌肉结构置于模拟应力,应变,和类似于在体内后肢肌肉中发现的机械环境的收缩活性;以及将所述构建体植入体内以用后肢的实际机械和生物化学环境包围所述构建体。我们的工作假设是,NMJ数量的增加与体外应用的电活动相结合,将导致肌肉和肌腱中更高级的表型,工程肌肉中的力产生增加,以及更强大和更发达的组织界面。体外工程构建体的体内植入将进一步促进所有组织和组织界面的表型和功能。该项目将针对以下具体目标:具体目标1。设计和制造具有功能性MTJ和NMJ的神经-肌腱-肌肉结构,并在三个开发时间点评估结构和功能的完整性。具体目标2。开发一种导管系统,以引导多个神经延伸向肌肉结构生长,从而增加结构的神经支配率。具体目标3。评价电刺激引起的肌肉收缩对神经-肌腱-肌肉结构和功能的影响。具体目标4。评价体内植入宿主动物后4周对神经-肌腱结构和功能的影响。
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 }}
LISA M LARKIN其他文献
LISA M LARKIN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('LISA M LARKIN', 18)}}的其他基金
Planning for clinical trial of fully-biologic, cell generated graft (CGEM) for ACLrepair
规划用于 ACL 修复的全生物细胞生成移植物 (CGEM) 的临床试验
- 批准号:
10724487 - 财政年份:2023
- 资助金额:
$ 8.62万 - 项目类别:
Non-Invasive, Quantitative, and Label-Free Characterization of Tissue Engineered Skeletal Muscle
组织工程骨骼肌的非侵入性、定量和无标记表征
- 批准号:
9894756 - 财政年份:2019
- 资助金额:
$ 8.62万 - 项目类别:
Utilization of Engineered Skeletal Muscle Units to Repair Volumetric Muscle
利用工程骨骼肌单位修复体积肌
- 批准号:
9198665 - 财政年份:2015
- 资助金额:
$ 8.62万 - 项目类别:
Utilization of Engineered Skeletal Muscle Units to Repair Volumetric Muscle
利用工程骨骼肌单位修复体积肌
- 批准号:
9274917 - 财政年份:2015
- 资助金额:
$ 8.62万 - 项目类别:
Engineering Innervated Muscle-Tendon Constructs for Tissue Regeneration
工程神经支配的肌肉肌腱结构用于组织再生
- 批准号:
8046434 - 财政年份:2007
- 资助金额:
$ 8.62万 - 项目类别:
Engineering Innervated Muscle-Tendon Constructs for Tissue Regeneration
工程神经支配的肌肉肌腱结构用于组织再生
- 批准号:
7758217 - 财政年份:2007
- 资助金额:
$ 8.62万 - 项目类别:
Electromechanical Stimuli on the Development of Engineered Myotendinous Junction
机电刺激对工程化肌腱接头发育的影响
- 批准号:
7177233 - 财政年份:2007
- 资助金额:
$ 8.62万 - 项目类别:
Engineering Innervated Muscle-Tendon Constructs for Tissue Regeneration
工程神经支配的肌肉肌腱结构用于组织再生
- 批准号:
7574397 - 财政年份:2007
- 资助金额:
$ 8.62万 - 项目类别:
Engineering Innervated Muscle-Tendon Constructs for Tissue Regeneration
工程神经支配的肌肉肌腱结构用于组织再生
- 批准号:
7241958 - 财政年份:2007
- 资助金额:
$ 8.62万 - 项目类别:
Engineering Innervated Muscle-Tendon Constructs for Tissue Regeneration
工程神经支配的肌肉肌腱结构用于组织再生
- 批准号:
7405408 - 财政年份:2007
- 资助金额:
$ 8.62万 - 项目类别:
相似海外基金
Spatiotemporal dynamics of acetylcholine activity in adaptive behaviors and response patterns
适应性行为和反应模式中乙酰胆碱活性的时空动态
- 批准号:
24K10485 - 财政年份:2024
- 资助金额:
$ 8.62万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Structural studies into human muscle nicotinic acetylcholine receptors
人体肌肉烟碱乙酰胆碱受体的结构研究
- 批准号:
MR/Y012623/1 - 财政年份:2024
- 资助金额:
$ 8.62万 - 项目类别:
Research Grant
CRCNS: Acetylcholine and state-dependent neural network reorganization
CRCNS:乙酰胆碱和状态依赖的神经网络重组
- 批准号:
10830050 - 财政年份:2023
- 资助金额:
$ 8.62万 - 项目类别:
Study on biological significance of acetylcholine and the content in food resources
乙酰胆碱的生物学意义及其在食物资源中的含量研究
- 批准号:
23K05090 - 财政年份:2023
- 资助金额:
$ 8.62万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
alpha7 nicotinic acetylcholine receptor allosteric modulation and native structure
α7烟碱乙酰胆碱受体变构调节和天然结构
- 批准号:
10678472 - 财政年份:2023
- 资助金额:
$ 8.62万 - 项目类别:
Diurnal Variation in Acetylcholine Modulation of Dopamine Dynamics Following Chronic Cocaine Intake
慢性可卡因摄入后乙酰胆碱对多巴胺动力学调节的昼夜变化
- 批准号:
10679573 - 财政年份:2023
- 资助金额:
$ 8.62万 - 项目类别:
Striatal Regulation of Cortical Acetylcholine Release
纹状体对皮质乙酰胆碱释放的调节
- 批准号:
10549320 - 财政年份:2022
- 资助金额:
$ 8.62万 - 项目类别:
Differential Nicotinic Acetylcholine Receptor Modulation of Striatal Dopamine Release as a Mechanism Underlying Individual Differences in Drug Acquisition Rates
纹状体多巴胺释放的烟碱乙酰胆碱受体差异调节是药物获取率个体差异的机制
- 批准号:
10553611 - 财政年份:2022
- 资助金额:
$ 8.62万 - 项目类别:
Mechanisms of nicotinic acetylcholine receptor modulation of cocaine reward
烟碱乙酰胆碱受体调节可卡因奖赏的机制
- 批准号:
10672207 - 财政年份:2022
- 资助金额:
$ 8.62万 - 项目类别:
Structural basis of nicotinic acetylcholine receptor gating and toxin inhibition
烟碱乙酰胆碱受体门控和毒素抑制的结构基础
- 批准号:
10848770 - 财政年份:2022
- 资助金额:
$ 8.62万 - 项目类别: