Photopolymerization-Induced Topography Directs Neurite and Schwann Cell Alignment
光聚合诱导的形貌引导神经突和雪旺细胞对齐
基本信息
- 批准号:8503972
- 负责人:
- 金额:$ 30万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-03-04 至 2018-02-28
- 项目状态:已结题
- 来源:
- 关键词:Acoustic NerveAdhesionsAntibodiesAuditoryAxonBindingBiochemicalBiocompatibleBiological AssayBiomedical EngineeringBiosensorCell AdhesionCellsClinicalCochlear ImplantsComplexCuesCyclic AMPCyclic GMPCyclic NucleotidesDataDominant-Negative MutationEffectivenessElectric StimulationElectrodesEnvironmentFailureFluorescence Resonance Energy TransferFutureGrowthHearingHearing Impaired PersonsImmunoblottingImplanted ElectrodesIn SituLengthLightMechanicsMediatingMediator of activation proteinMethacrylatesModelingMolecularMorphologyMusicNatural regenerationNerveNerve FibersNerve RegenerationNeuritesNeurogliaNeuronsNeurophysiology - biologic functionOutcome MeasurePatientsPatternPerformancePeriodicityPeripheralPhosphorylationPolymersProcessPropertyProsthesisProtein IsoformsRadialRadiation DosageReactionResolutionRho-associated kinaseSchwann CellsSecond Messenger SystemsSignal TransductionSourceStaining methodStainsSurfaceSystemTechnologyTissuesUltraviolet RaysWettabilityWorkbasecell growthcrosslinkdensitydesignimprintimprovedin vivolight intensitymimicrynanoscalenerve supplyneural prosthesisneuroprosthesisnew technologyphotopolymerizationprimary outcomepublic health relevancerelating to nervous systemrepairedresponsescaffoldsecond messengersecondary outcomesmall moleculespiral ganglion
项目摘要
DESCRIPTION (provided by applicant): Poor integration with target tissue significantly limits the effectiveness of nearly all neural prostheses. For example, cochlear implant (CI) recipients perform poorly with complex auditory tasks due to poor spatial and temporal resolution provided by the neural-electrode interface. Directing growth of spiral ganglion neuron (SGN) neurites into close proximity, or even contact, with the stimulating electrodes would likely improve spatial and temporal resolution and increase performance. To be useful, regrowth must be radial and directed towards the source of stimulation, recapitulating normal afferent cochlear innervation. To develop and understand technology designed to guide SGN neurite and Schwann cell (SC) growth, photopolymerization (PP), i.e. the formation of polymers using light, was used to create microchannels in biocompatible methacrylate polymers. These surface topographic features robustly guide SGN neurite and SGSC growth. We hypothesize that the ability of these physical cues to direct SGN neurite and SGSC alignment depends on specific surface topographic features and material properties and results from tuning of intracellular signals including RhoA and Rho associated kinase (ROCK). In response to BRG PA10-009, the work in this proposal is both design- and hypothesis-driven. In aim 1 the excellent spatial reaction control afforded by PP will be leveraged to fabricate parallel line-space gratings with varied amplitude, periodicity, and surface nanoroughness. The extent to which these topographic features influence neurite and glial cell adhesion, survival and alignment to the pattern will then be determined. As cell-material interactions depend on substrate surface and mechanical properties in addition to surface topography, aim 2 determines the survival and morphological responses of neurons and glia to varied surface (e.g. polarity) and mechanical (e.g. stiffness) properties. Finally, aim 3 examines the contribution of RhoA/ROCK, key mediators of neurite guidance by chemorepulsive cues, to neurite and SC alignment to micropatterns. It also seeks to characterize second messenger systems including the cyclic nucleotides, cAMP and cGMP, that mediate neurite and SC alignment and RhoA/ROCK activity in response to surface topographies. The results of these studies will be among the first to define the basic mechanisms by which cells sense and respond to specific surface topographies and material properties. Furthermore, they will identify the topographic features and material properties necessary for future fabrication of scaffolds that can be used for in vivo neural regeneration models including the design of enhanced neuron:prosthesis interfaces.
描述(由申请人提供):与目标组织的整合不良显着限制了几乎所有神经假体的有效性。例如,由于神经电极接口提供的空间和时间分辨率差,耳蜗植入(CI)接受者在复杂的听觉任务中表现不佳。将螺旋神经节神经元(SGN)神经突的生长引导到与刺激电极紧密接近或甚至接触可能会提高空间和时间分辨率并提高性能。为了有用,再生长必须是放射状的,并且指向刺激源,重现正常的传入耳蜗神经支配。为了开发和理解旨在引导SGN神经突和许旺细胞(SC)生长的技术,使用光聚合(PP),即使用光形成聚合物,在生物相容性甲基丙烯酸酯聚合物中创建微通道。这些表面地形特征有力地引导SGN神经突和SGSC生长。我们假设这些物理线索指导SGN神经突和SGSC对齐的能力取决于特定的表面形貌特征和材料特性,以及调节包括RhoA和Rho相关激酶(ROCK)在内的细胞内信号的结果。作为对BRG PA 10 -009的回应,本提案中的工作是设计和假设驱动的。在目标1中,将利用PP提供的出色的空间反应控制来制造具有不同振幅、周期性和表面纳米粗糙度的平行线间距光栅。然后将确定这些地形特征影响神经突和神经胶质细胞粘附、存活和与图案对齐的程度。由于细胞与材料的相互作用除了表面形貌之外还取决于基底表面和机械特性,因此目标2决定了神经元和神经胶质细胞对不同表面(例如极性)和机械(例如刚度)特性的存活和形态反应。最后,目的3检查RhoA/ROCK的贡献,神经突引导的化学排斥性线索的关键介质,神经突和SC对齐的微模式。它还试图表征第二信使系统,包括环核苷酸,cAMP和cGMP,介导神经突和SC对齐和RhoA/ROCK活性响应于表面形貌。这些研究的结果将是第一个定义细胞感知和响应特定表面形貌和材料特性的基本机制。此外,他们将确定未来制造支架所需的地形特征和材料特性,这些支架可用于体内神经再生模型,包括增强神经元:假体界面的设计。
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 }}
Allan Guymon其他文献
Allan Guymon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('Allan Guymon', 18)}}的其他基金
Photopolymerization-Induced Topography Directs Neurite and Schwann Cell Alignment
光聚合诱导的形貌引导神经突和雪旺细胞对齐
- 批准号:
8628102 - 财政年份:2013
- 资助金额:
$ 30万 - 项目类别:
Reduction of Intracochlear Trauma and Fibrosis Using Dual Network, Zwitterionic Hydrogel Thin Films on Cochlear Implant Surfaces
使用人工耳蜗表面上的双网络两性离子水凝胶薄膜减少耳蜗内创伤和纤维化
- 批准号:
10659699 - 财政年份:2013
- 资助金额:
$ 30万 - 项目类别:
Photopolymerization-Induced Topography Directs Neurite and Schwann Cell Alignment
光聚合诱导的形貌引导神经突和雪旺细胞对齐
- 批准号:
9012816 - 财政年份:2013
- 资助金额:
$ 30万 - 项目类别:
Reduction of intracochlear fibrosis and bacterial infection using photopolymerized durable zwitterionic coatings on cochlear implant biomaterials
使用人工耳蜗生物材料上的光聚合耐用两性离子涂层减少耳蜗内纤维化和细菌感染
- 批准号:
10348137 - 财政年份:2013
- 资助金额:
$ 30万 - 项目类别:
相似海外基金
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y004841/1 - 财政年份:2024
- 资助金额:
$ 30万 - 项目类别:
Research Grant
Defining a role for non-canonical mTORC1 activity at focal adhesions
定义非典型 mTORC1 活性在粘着斑中的作用
- 批准号:
BB/Y001427/1 - 财政年份:2024
- 资助金额:
$ 30万 - 项目类别:
Research Grant
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y005414/1 - 财政年份:2024
- 资助金额:
$ 30万 - 项目类别:
Research Grant
Development of a single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions.
开发一次性、即用型、无菌、双室、双注射器可喷雾水凝胶,以防止术后心脏粘连。
- 批准号:
10669829 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10587090 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Improving Maternal Outcomes of Cesarean Delivery with the Prevention of Postoperative Adhesions
通过预防术后粘连改善剖宫产的产妇结局
- 批准号:
10821599 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10841832 - 财政年份:2023
- 资助金额:
$ 30万 - 项目类别:
Prevention of Intraabdominal Adhesions via Release of Novel Anti-Inflammatory from Surface Eroding Polymer Solid Barrier
通过从表面侵蚀聚合物固体屏障中释放新型抗炎剂来预防腹内粘连
- 批准号:
10532480 - 财政年份:2022
- 资助金额:
$ 30万 - 项目类别:
I-Corps: A Sprayable Tissue-Binding Hydrogel to Prevent Postsurgical Cardiac Adhesions
I-Corps:一种可喷雾的组织结合水凝胶,可防止术后心脏粘连
- 批准号:
10741261 - 财政年份:2022
- 资助金额:
$ 30万 - 项目类别:
Sprayable Polymer Blends for Prevention of Site Specific Surgical Adhesions
用于预防特定部位手术粘连的可喷涂聚合物共混物
- 批准号:
10674894 - 财政年份:2022
- 资助金额:
$ 30万 - 项目类别: