Hybrid Hydrogel Biomaterials Comprising Clickable Decellularized Extracellular Matrix for Engineering Dynamic 3D Models of Fibrosis
包含可点击脱细胞细胞外基质的混合水凝胶生物材料,用于工程纤维化动态 3D 模型
基本信息
- 批准号:10661783
- 负责人:
- 金额:$ 53.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-01 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAccelerationActinsAgeAlveolarAnimal ModelArchitectureAtomic Force MicroscopyBiocompatible MaterialsBiologicalCell CommunicationCell Culture TechniquesCellsChronicClinicalCollagenDataDepositionDiagnosisDiseaseDistalElderlyEncapsulatedEngineeringEpitheliumExperimental DesignsExposure toExtracellular MatrixFibroblastsFibrosisFoundationsFunctional disorderGasesGoalsHistologyHumanHybridsHydrogelsImageIn Situ HybridizationIn VitroLaboratoriesLifeLightLocationLungLung diseasesMechanicsMediatorMedicalMesenchymalMethodsMicrofabricationModelingModulusMolecularMorbidity - disease rateMusOutputPathogenesisPathologyPathway interactionsPatientsPhenotypePhysiologicalPhysiologyPlatelet-Derived Growth Factor alpha ReceptorPopulationPositioning AttributePrecision therapeuticsProteinsPulmonary FibrosisReactionReporterReproducibilityResearch PersonnelRespiratory FailureRheologySeverity of illnessSignal PathwaySmooth MuscleSourceStainsStatistical Data InterpretationStructureStructure of parenchyma of lungSurvival RateSystemTechnologyTestingTherapeuticTimeTissue SampleTissuesType II Epithelial Receptor CellVertebral columnWorkalveolar epitheliumantifibrotic treatmentbiomaterial compatibilitydesigndrug discoverydrug efficacyethylene glycolfibrotic lunghuman diseasehuman modelhuman tissueidiopathic pulmonary fibrosisimprovedin vitro Modelin vitro activityinnovationmechanical propertiesmortalitynew therapeutic targetnovelpre-clinicalprogramsprotein expressionresponsescreeningspatiotemporaltargeted treatmentthree dimensional cell culturethree-dimensional modelingtooltranscriptome sequencing
项目摘要
PROJECT SUMMARY
Fibrotic disorders account for a significant source of global morbidity and mortality. Idiopathic pulmonary
fibrosis (IPF) is a chronic, progressive, and life-threatening lung disease most prevalent in elderly populations.
IPF impacts 100,000 patients in the U.S. alone and there are approximately 34,000 new global diagnoses each
year. Most patients with IPF succumb to respiratory failure within 3-5 years and the only clinically available
therapeutic treatments do not cure the disease. As the average age of the U.S. population increases, it is
imperative for researchers and practitioners to work together to identify new targets to halt or reverse IPF.
Discovery of new therapeutic targets for IPF through traditional cell culture techniques and pre-clinical animal
models has several limitations because these systems do not adequately reproduce key aspects of human
physiology. Most importantly, dynamic cell-matrix and cell-cell interactions that are difficult to recapitulate in
vitro drive the progression of fibrosis: it is not clear, for example, whether changes in the extracellular matrix
(ECM) composition or the subsequent alterations in mechanical properties of the surrounding tissues are the
more potent drivers of IPF, i.e., the best target for therapeutics. New tools and technologies that enable us to
dynamically study the pathogenesis of fibrosis over time remain an unresolved challenge.
My laboratory has developed novel methods to synthesize and microfabricate a new class of biomaterials to
conduct dynamic cell-ECM studies, not currently possible in traditional models of fibrosis. Our innovative
platform combines a phototunable poly(ethylene glycol) (PEG) backbone with clickable decellularized ECM
(dECM) from healthy or diseased lung tissue so that we may decouple fibrotic tissue composition (e.g.,
increased collagen content) from subsequent changes in mechanical properties (e.g., increased stiffness).
Specifically, healthy or IPF lung dECM will be incorporated into soft (1-5 kPa) hydrogel matrices that mimic
healthy tissue, then exposure to focused light will dynamically initiate stiffening to fibrotic levels (>10 kPa).
Three aims are proposed to engineer and implement this biomaterials-based strategy for building novel, high-
fidelity in vitro models of IPF. AIM I: Engineer the structure, composition, and dynamic mechanics of PEG-
dECM cell culture platforms to recapitulate distal lung tissue; AIM II: Interrogate the impact of composition and
mechanical properties on fibroblast activation using dynamic PEG-dECM biomaterial platforms; and AIM III:
Identify druggable mechanosensitive targets of the fibrotic activity recreated in dynamic 3D models. Successful
completion of these aims will advance our understanding of the cellular and molecular drivers of IPF, building
the foundation for high-throughput discovery and screening of therapeutics for precision medical treatments.
项目总结
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
An Introduction to Engineering and Modeling the Lung.
肺工程和建模简介。
- DOI:10.1007/978-3-031-26625-6_1
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Tanneberger,AliciaE;Weiss,DanielJ;Magin,ChelseaM
- 通讯作者:Magin,ChelseaM
Engineering Dynamic 3D Models of Lung.
肺工程动态 3D 模型。
- DOI:10.1007/978-3-031-26625-6_9
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Blomberg,Rachel;Hewawasam,RukshikaS;Šerbedžija,Predrag;Saleh,Kamiel;Caracena,Thomas;Magin,ChelseaM
- 通讯作者:Magin,ChelseaM
Engineering Tissue-Informed Biomaterials to Advance Pulmonary Regenerative Medicine.
工程组织信息生物材料以促进肺部再生医学。
- DOI:10.3389/fmed.2021.647834
- 发表时间:2021
- 期刊:
- 影响因子:3.9
- 作者:Campbell DR Jr;Senger CN;Ryan AL;Magin CM
- 通讯作者:Magin CM
{{
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 }}
Chelsea M Magin其他文献
Chelsea M Magin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('Chelsea M Magin', 18)}}的其他基金
Hybrid Hydrogel Biomaterials Comprising Clickable Decellularized Extracellular Matrix for Engineering Dynamic 3D Models of Fibrosis
包含可点击脱细胞细胞外基质的混合水凝胶生物材料,用于工程纤维化动态 3D 模型
- 批准号:
10224335 - 财政年份:2020
- 资助金额:
$ 53.2万 - 项目类别:
Hybrid Hydrogel Biomaterials Comprising Clickable Decellularized Extracellular Matrix for Engineering Dynamic 3D Models of Fibrosis
包含可点击脱细胞细胞外基质的混合水凝胶生物材料,用于工程纤维化动态 3D 模型
- 批准号:
10026363 - 财政年份:2020
- 资助金额:
$ 53.2万 - 项目类别:
Engineering ex vivo models of lung cancer and chemoprevention
肺癌和化学预防的离体工程模型
- 批准号:
10038486 - 财政年份:2020
- 资助金额:
$ 53.2万 - 项目类别:
Hybrid Hydrogel Biomaterials Comprising Clickable Decellularized Extracellular Matrix for Engineering Dynamic 3D Models of Fibrosis
包含可点击脱细胞细胞外基质的混合水凝胶生物材料,用于工程纤维化动态 3D 模型
- 批准号:
10454853 - 财政年份:2020
- 资助金额:
$ 53.2万 - 项目类别:
Advanced Micro-patterned Wound Dressings for Enhanced Epithelialization
用于增强上皮化的先进微图案伤口敷料
- 批准号:
8832483 - 财政年份:2014
- 资助金额:
$ 53.2万 - 项目类别:
Hydrogel Scaffolds with Engineered Dynamically Tunable Topographies for hMSC Diff
具有用于 hMSC Diff 的工程动态可调拓扑的水凝胶支架
- 批准号:
8199807 - 财政年份:2011
- 资助金额:
$ 53.2万 - 项目类别:
Hydrogel Scaffolds with Engineered Dynamically Tunable Topographies for hMSC Diff
具有用于 hMSC Diff 的工程动态可调拓扑的水凝胶支架
- 批准号:
8333062 - 财政年份:2011
- 资助金额:
$ 53.2万 - 项目类别:
相似海外基金
EXCESS: The role of excess topography and peak ground acceleration on earthquake-preconditioning of landslides
过量:过量地形和峰值地面加速度对滑坡地震预处理的作用
- 批准号:
NE/Y000080/1 - 财政年份:2024
- 资助金额:
$ 53.2万 - 项目类别:
Research Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328975 - 财政年份:2024
- 资助金额:
$ 53.2万 - 项目类别:
Continuing Grant
SHINE: Origin and Evolution of Compressible Fluctuations in the Solar Wind and Their Role in Solar Wind Heating and Acceleration
SHINE:太阳风可压缩脉动的起源和演化及其在太阳风加热和加速中的作用
- 批准号:
2400967 - 财政年份:2024
- 资助金额:
$ 53.2万 - 项目类别:
Standard Grant
Market Entry Acceleration of the Murb Wind Turbine into Remote Telecoms Power
默布风力涡轮机加速进入远程电信电力市场
- 批准号:
10112700 - 财政年份:2024
- 资助金额:
$ 53.2万 - 项目类别:
Collaborative R&D
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328973 - 财政年份:2024
- 资助金额:
$ 53.2万 - 项目类别:
Continuing Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328972 - 财政年份:2024
- 资助金额:
$ 53.2万 - 项目类别:
Continuing Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
- 批准号:
2332916 - 财政年份:2024
- 资助金额:
$ 53.2万 - 项目类别:
Standard Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
- 批准号:
2332917 - 财政年份:2024
- 资助金额:
$ 53.2万 - 项目类别:
Standard Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328974 - 财政年份:2024
- 资助金额:
$ 53.2万 - 项目类别:
Continuing Grant
Study of the Particle Acceleration and Transport in PWN through X-ray Spectro-polarimetry and GeV Gamma-ray Observtions
通过 X 射线光谱偏振法和 GeV 伽马射线观测研究 PWN 中的粒子加速和输运
- 批准号:
23H01186 - 财政年份:2023
- 资助金额:
$ 53.2万 - 项目类别:
Grant-in-Aid for Scientific Research (B)