Engineering multifaceted 3D human organ platforms for toxicity testing
设计用于毒性测试的多层面 3D 人体器官平台
基本信息
- 批准号:10675647
- 负责人:
- 金额:$ 39.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-24 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAccelerationAddressAdrenal GlandsAdrenal MedullaAnimal ModelAutomobile DrivingAutonomic nervous systemAwardBiocompatible MaterialsBiological AssayBiomedical ResearchBlood VesselsCardiacCardiac MyocytesCardiovascular ModelsCardiovascular systemCell CommunicationCellsChromaffin CellsClinicalClinical TrialsDevelopmentEndotheliumEngineeringEquilibriumEquipmentGoalsHealthcareHumanIn VitroLasersMeasuresMethodsMicrofabricationMicrofluidicsModelingMyocardiumNeuronsOrganOxygenPhysiologicalPlumbingScientific Advances and AccomplishmentsSmooth MuscleStatistical ModelsStructureSystemTechniquesTestingTherapeuticTimeTissuesToxic effectToxicity TestsWorkbioelectricitybioelectronicsdesignfabricationimprovedinnovationinnovative technologiesinstrumentinstrumentationlithographymicrophysiology systemnerve supplyneuralpharmacologicpolydimethylsiloxaneresponsescreeningsexstem cell differentiationthree dimensional cell culturetool
项目摘要
PROJECT SUMMARY
This award will accelerate my long-term goal to develop microphysiological systems to improve human
pharmacological efficacy with reduced toxicity and reliance on small animal models. Models of the
cardiovascular system (vascular, myocardium, adrenal medulla) in vitro have primarily been limited to simplified
2D structures and have not evaluated for tissue-tissue interactions. As such, the structure/function relationships,
and the cell-cell interactions driven by tissue organization and innervation remain poorly understood. Thus, MPS
that recapitulates key components of the human cardiovascular system, including physiologically relevant shear
flow, oxygen saturation, bioelectric stimulation, primary human endothelial, smooth muscle, cardiomyocytes,
chromaffin cells, and human autonomic neurons would be a valuable tool for advancing scientific discovery,
healthcare, compound screening, and biomedical research. Current MPS generally utilize specialized equipment
and traditional microfabrication techniques via soft lithography with polydimethylsiloxane (PDMS), making
microfluidic plumbing difficult as well as nearly impossible control of oxygen, and potential for analyte loss.
Therefore, new fabrication approaches that deviate from PDMS are needed. Our approach here describes the
application of a laser-fabricated, cut and assembled MPS for a fully humanized system. There is a scientific
and clinical urgency for the development of new tools to identify compound toxicity and decrease new
compound attrition during clinical trials. By applying my strengths in biomaterials, organ-chip design,
bioelectronics, and neuroengineering, we will accelerate the development of robust 3D, instrumented MPS
platforms of the cardiovascular system. A fundamental issue addressed in this project will be the ability to
integrate, in a scalable platform, instrumentation for stimulation and recording of neural, adrenal, and cardiac
activity to better elucidate the impact of the autonomic nervous system and compound toxicity. We will harness
a statistical model to identify driving factors in cell fate, function, and identify sex-based differential responses in
autonomic balance on the MPS. These innovative models will integrate recent advances in stem cell
differentiation and our proven ‘cut & assemble’ fabrication method to broadly disseminate these organ platforms.
项目总结
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on the host in a gut microphysiological system.
- DOI:10.1016/j.celrep.2023.113481
- 发表时间:2023-12-26
- 期刊:
- 影响因子:8.8
- 作者:
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Ryan Alan Koppes其他文献
Ryan Alan Koppes的其他文献
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{{ truncateString('Ryan Alan Koppes', 18)}}的其他基金
Engineering multifaceted 3D human organ platforms for toxicity testing
设计用于毒性测试的多层面 3D 人体器官平台
- 批准号:
10275117 - 财政年份:2021
- 资助金额:
$ 39.25万 - 项目类别:
Engineering multifaceted 3D human organ platforms for toxicity testing
设计用于毒性测试的多层面 3D 人体器官平台
- 批准号:
10493263 - 财政年份:2021
- 资助金额:
$ 39.25万 - 项目类别:
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