Directing Collective Epithelial Morphology in Space and Time Using a Light-Based Carving Tool
使用基于光的雕刻工具指导空间和时间上的集体上皮形态
基本信息
- 批准号:9809041
- 负责人:
- 金额:$ 15.4万
- 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:3-DimensionalAblationAcinus organ componentAcuteAffectAgingArchitectureAutoimmune ResponsesBasement membraneBiologicalBiomanufacturingCaliberCell Culture TechniquesCell ProliferationCell SizeCell SurvivalCellsCellular MorphologyCellular SpheroidsCessation of lifeClinicalCoculture TechniquesComplexConnective TissueCrosslinkerCuesDental CareDental cariesDepositionDevelopmentDiseaseDuct (organ) structureDuctalElementsEncapsulatedEngineeringEpithelialEpitopesEtiologyExtracellular MatrixFaceFeasibility StudiesFibroblastsFinancial HardshipFutureGelGlandGoalsGrantGrowthGrowth FactorHarvestHead and Neck CancerHumanHyaluronic AcidHydrogelsIn VitroIntegrinsLaboratoriesLasersLengthLigandsLightMajor salivary gland structureMapsMatrix MetalloproteinasesMembrane ProteinsMesenchymalMethodsMicroscopyMorphologyMyoepithelialNeuronsNeurotransmitter ReceptorNeurotransmittersOral healthOrganPainPalliative CarePathway interactionsPatientsPatternPeptide Signal SequencesPhenotypePhysicsPilot ProjectsPolymersPorosityPositioning AttributePrintingProliferatingQuality of lifeRadialRadiation induced damageRadiation therapyRegenerative MedicineResolutionSalivarySalivary Gland TissueSalivary GlandsShapesSignal TransductionSjogren&aposs SyndromeSourceStem cellsStructureStudy modelsSyringesSystemTechnologyTestingTherapeuticTimeTissue EngineeringTissuesTravelVariantWorkXerostomiaabsorptionbasebiomaterial compatibilitybioprintingcell growthcell motilitycell typecostcrosslinkimplantable deviceimplantationimprovedlithographymigrationmonolayernew technologynovelprogenitorprototypereconstitutionreduce symptomsregenerative therapyresponsesalivary acinar cellsalivary assaysalivary cellstandard of carestemtemporal measurementthree dimensional cell culturetime usetooltwo-photon
项目摘要
Project Summary:
Xerostomia, or “dry mouth”, is a challenging clinical condition, caused by damage to the cells of the salivary
gland. It may result from a variety of tissue insults, including acute damage from radiation therapy for head and
neck cancers, progressive auto-immune response in Sjogren’s disease, or other unknown etiology from aging.
Current treatments offer only temporary relief of symptoms, and poor resolution of associated oral health
decay. The cost of this condition is considerable, both in quality of life and the financial burden of increased
dental care. The fields of tissue engineering and regenerative medicine offer many tools for the potential
reconstitution of healthy salivary-derived cells within supportive hydrogel matrices, but few of these options
provide sufficient spatial and temporal resolution to restore the complex branched structure and precise spatial
phenotype map of the major salivary glands. However, new discoveries in laser-based hydrogel degradation
(LBHD) can be used to “carve” pathways through intact hydrogel slabs, with pinpoint, subcellular resolution in
xyz, and offer a method to guide a growing salivary epithelial bud in 3 dimensions. Our hypothesis for the
present proposal is that we can use multiphoton-based LBHD to elongate a multicellular cluster in a given
direction, and recreate key elements of the native gland. To do this, we will employ our laboratory’s expertise in
isolation of primary human salivary-derived stem/progenitor cells (hS/PCs) from healthy tissues, and
encapsulation as responsive 3D multicellular spheroid clusters within customizable, biocompatible hyaluronic
acid (HA) hydrogels. Our ongoing work has shown that, by tailoring the porosity of these hydrogels and their
concentration of bioactive epitopes, we can impact cluster size, morphology, and interaction with the
surrounding extracellular matrix. We will test our hypothesis through the following Specific Aims:
Aim 1. Establish parameters to carve “tunnels” through HA hydrogels and promote HS/PC cluster ingrowth.
Aim 2. Adapt the system to alternate matrices that enable fibroblast co-culture, or incorporate photolabile
crosslinkers for easier fabrication. Aim 3. Assess phenotype of the growing cluster, at its trailing and leading
edges and branched termini, for signs of differentiated phenotype. If successful, this system could serve as a
useful model for studying mechanisms of human salivary cell organization and differentiation; the system might
also be an early prototype for manufacturing tissue engineered gland replacements. The R03 mechanism will
provide support for the necessary pilot and feasibility studies, to demonstrate that these proven technologies
can be combined to produce a novel platform.
项目总结:
口干症,或“口干”,是一种极具挑战性的临床症状,由唾液细胞受损引起。
腺体。它可能是由各种组织损伤引起的,包括头部和头部放射治疗的急性损伤
宫颈癌,干燥病的进行性自身免疫反应,或其他因年龄增长而导致的不明原因。
目前的治疗方法只能暂时缓解症状,而且对相关的口腔健康的解决效果很差。
腐烂。这种情况的代价是相当大的,无论是在生活质量方面,还是在增加的经济负担方面
牙科护理。组织工程和再生医学领域为实现这一潜力提供了许多工具
在支持性水凝胶基质中重建健康的唾液来源细胞,但这些选择很少
提供足够的空间和时间分辨率,以恢复复杂的分支结构和精确的空间
主要唾液腺的表型图谱。然而,激光水凝胶降解方面的新发现
(LBHD)可以用来在完整的水凝胶片中“切割”路径,具有精确的亚细胞分辨率
XYZ,并提供了一种三维引导唾液上皮芽生长的方法。我们的假设是
目前的建议是,我们可以使用基于多光子的LBHD来拉长给定的多细胞簇
方向,并重新创造了本土腺体的关键元素。为此,我们将利用我们实验室的专业知识
从健康组织中分离原代人类唾液来源的干细胞/祖细胞(HS/PC),以及
在可定制、生物兼容的透明质酸内封装为响应性3D多细胞球状簇
酸(HA)水凝胶。我们正在进行的工作表明,通过定制这些水凝胶的孔隙率和它们的
生物活性表位的浓度,我们可以影响簇的大小、形态以及与
周围的细胞外基质。我们将通过以下具体目标来验证我们的假设:
目的1.建立参数,通过羟基磷灰石水凝胶开凿“隧道”,促进HS/PC集群的生长。
目标2.使该系统适应于支持成纤维细胞共培养的替代基质,或结合耐光性
更容易制造的交联剂。目标3.评估正在成长的集群的表型,在其尾随和领先
边缘和分枝的末端,为分化表型的迹象。如果成功,这个系统可以作为一种
研究人类唾液细胞组织和分化机制的有用模型;该系统可能
也是制造组织工程化腺体替代物的早期原型。R03机制将
为必要的试点和可行性研究提供支持,以证明这些经过验证的技术
可以组合在一起生产出一种新颖的平台。
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 }}
Daniel A Harrington其他文献
Daniel A Harrington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('Daniel A Harrington', 18)}}的其他基金
相似海外基金
Targeted ablation of cerebral atherosclerosis using supramolecular self-assembly
利用超分子自组装靶向消融脑动脉粥样硬化
- 批准号:
24K21101 - 财政年份:2024
- 资助金额:
$ 15.4万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
心房細動に対するPulsed Field Ablationの組織創傷治癒過程を明らかにする網羅的研究
阐明房颤脉冲场消融组织伤口愈合过程的综合研究
- 批准号:
24K11201 - 财政年份:2024
- 资助金额:
$ 15.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
遅延造影心臓MRIによる心房細動Ablation冷却効果の比較:28 vs. 31 mm Cryoballoon
使用延迟对比增强心脏 MRI 比较房颤消融冷却效果:28 毫米与 31 毫米 Cryoballoon
- 批准号:
24K11281 - 财政年份:2024
- 资助金额:
$ 15.4万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
InSPACE-VT_Development and Validation of Virtual Pace Mapping to Guide Catheter Ablation of Ventricular Tachycardia
InSPACE-VT_虚拟起搏测绘的开发和验证以指导室性心动过速导管消融
- 批准号:
EP/Z001145/1 - 财政年份:2024
- 资助金额:
$ 15.4万 - 项目类别:
Fellowship
CAREER: Heat Penetration Depth and Direction Control with Closed-Loop Device for Precision Ablation
职业:利用闭环装置控制热穿透深度和方向,实现精确烧蚀
- 批准号:
2338890 - 财政年份:2024
- 资助金额:
$ 15.4万 - 项目类别:
Continuing Grant
Collaborative Research: RUI: Frontal Ablation Processes on Lake-terminating Glaciers and their Role in Glacier Change
合作研究:RUI:湖终止冰川的锋面消融过程及其在冰川变化中的作用
- 批准号:
2334777 - 财政年份:2024
- 资助金额:
$ 15.4万 - 项目类别:
Continuing Grant
Collaborative Research: RUI: Frontal Ablation Processes on Lake-terminating Glaciers and their Role in Glacier Change
合作研究:RUI:湖终止冰川的锋面消融过程及其在冰川变化中的作用
- 批准号:
2334775 - 财政年份:2024
- 资助金额:
$ 15.4万 - 项目类别:
Continuing Grant
Collaborative Research: RUI: Frontal Ablation Processes on Lake-terminating Glaciers and their Role in Glacier Change
合作研究:RUI:湖终止冰川的锋面消融过程及其在冰川变化中的作用
- 批准号:
2334776 - 财政年份:2024
- 资助金额:
$ 15.4万 - 项目类别:
Continuing Grant
Cryo laser-ablation system (157+193nm) with 'triple-quad' plasma mass spectrometer, Cryo-LA-ICPMS/MS
带有“三重四极杆”等离子体质谱仪、Cryo-LA-ICPMS/MS 的冷冻激光烧蚀系统 (157 193nm)
- 批准号:
515081333 - 财政年份:2023
- 资助金额:
$ 15.4万 - 项目类别:
Major Research Instrumentation
MRI: Acquisition of a Laser Ablation - Inductively Coupled Plasma - Triple Quadrupole - Mass Spectrometer (LA-ICP-QQQ-MS) System For Research and Education
MRI:获取用于研究和教育的激光烧蚀 - 电感耦合等离子体 - 三重四极杆 - 质谱仪 (LA-ICP-MS/MS) 系统
- 批准号:
2320040 - 财政年份:2023
- 资助金额:
$ 15.4万 - 项目类别:
Standard Grant