Characterization of an Ex Vivo Bioprinted Skin Model of Sulfur Mustard Injury
硫芥损伤离体生物打印皮肤模型的表征
基本信息
- 批准号:10228424
- 负责人:
- 金额:$ 5万
- 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:2020-09-17 至 2021-11-17
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAddressAdherenceAdipocytesAffectAnatomyAnimal ModelAnimalsAreaBasement membraneBiochemicalBiologicalBiological MarkersBiomedical EngineeringBiomedical ResearchBiomimeticsBullaBurn injuryCD14 geneCell Culture TechniquesCell DeathCellsCessation of lifeChemical ModelsChemical Warfare AgentsChemical WeaponsChemicalsCicatrixClinicalCollagen Type VIIComplexDataDermalDermatologicDevelopmentDiseaseDoseEdemaElementsEndothelial CellsEpidermal RidgesEpidermisErythemaExposure toFibroblastsFunctional disorderFundingGene ExpressionGenetic TranscriptionGoalsHistologicHumanIn VitroInflammationInflammation MediatorsInjuryInvestigationMetalloproteasesMilitary PersonnelModalityModelingMustard GasOrganOrganoidsPathologicPathway interactionsPhysiologicalPhysiologyPigmentation physiologic functionPoly(ADP-ribose) PolymerasesPopulationPre-Clinical ModelProtein AnalysisQuantitative Reverse Transcriptase PCRRNA analysisResearch InstituteScanning Electron MicroscopySignaling MoleculeSkinSkin injuryStructural ProteinStructureSystemTechniquesTestingTimeTissue EngineeringTissuesToxic effectTreatment EfficacyValidationVascularizationVesicantsWorld War Ibasebioprintingbioweaponcell typecytokinecytotoxicityextracellularhealingimprovedin vitro Modelkeratinocytelaminin-5medical countermeasuremelanocytemonocytenovelorganizational structurepre-clinicalprotein expressionprototypereal time monitoringresearch studyresponseskin barrierthree dimensional structuretwo-dimensional
项目摘要
PROJECT SUMMARY
Sulfur Mustard (SM) remains a significant threat to civilian and military populations. Skin exposure to SM induces
erythema, followed by edema and large blisters in the affected area, with prolonged healing times. The sequence
and manner of cell death and detachment in this injury are still unresolved, in part due to incomplete in vitro and
preclinical models. Since the goal of an ex vivo 3D skin model is to replicate the authentic anatomy and
physiology of native skin, there is an immense need to develop bioengineered skin with multiple cell types and
appropriate physiological potential. Assessment of bioprinted skin as an ex vivo organoid (organ tissue
equivalent) has demonstrated that it maintains its layered structure for over 2 months in vitro. Assessment of
skin organoids by RNA and protein analysis demonstrate a physiological response similar to those seen in
normal human skin. These encouraging results suggest that this skin construct is recapitulating the human organ
and we propose to use the funds available through this supplement to further expand the bioprinted human skin
into a model of chemical burn injuries. We will use bioprinted skin to model exposure to the known chemical
vesicant sulfur mustard (SM), with the ultimate goal of showing the full utility of the bioprinted skin in elucidating
biochemical and pathophysiological pathways in an effort to discover biomarkers and medical countermeasures.
Based on the data we have generated to date, our central hypothesis is that ex vivo bioprinted skin will
model clinical pathological effects of exposure to the chemical vesicant sulfur mustard. The overall goal
of this supplemental proposal is to generate proof of principal data showing that the bioprinted skin will respond
to the chemical insult in a way that is consistent with the known effects of SM. Our study will validate the dose
and time of exposure for modeling the human response to SM in vitro, and will include histological, qRT-PCR,
and ELIZA analysis. These studies will focus on demonstrating that the bioprinted skin behaves in a way that is
consistent with Specific Aim 1 will characterize the pathological consequences of sulfur mustard exposure.
Specific Aim 2 will look to identify cellular pathways affected by SM induced injury. These studies will validate
the use of the bioprinted skin as a viable ex vivo model of SM toxicity which will enable high precision analysis,
including real-time monitoring and -omics to elucidate the sequence and mechanism of sulfur mustard skin
injuries. Furthermore, it suggests that the bioprinted skin can be developed into a general surrogate of human
skin pathophysiology useful in studying other types of insults. Ultimately, we believe that this system will identify
biomarkers of exposure and therapeutic efficacy, as well as serving as a useful modality to discovery and
optimize medical countermeasures for a range of chemical and biological weapons.
项目总结
项目成果
期刊论文数量(0)
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ADAM JORGENSEN其他文献
ADAM JORGENSEN的其他文献
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{{ truncateString('ADAM JORGENSEN', 18)}}的其他基金
Integration And Remodeling Of Bioprinted Skin In Full-Thickness Wound Healing
生物打印皮肤在全层伤口愈合中的整合和重塑
- 批准号:
10316225 - 财政年份:2019
- 资助金额:
$ 5万 - 项目类别:
Integration And Remodeling Of Bioprinted Skin In Full-Thickness Wound Healing
生物打印皮肤在全层伤口愈合中的整合和重塑
- 批准号:
10525225 - 财政年份:2019
- 资助金额:
$ 5万 - 项目类别:
Integration and Remodeling of Bioprinted Skin in Full-Thickness Wound Healing
生物打印皮肤在全层伤口愈合中的整合和重塑
- 批准号:
10414508 - 财政年份:2019
- 资助金额:
$ 5万 - 项目类别:
Integration And Remodeling Of Bioprinted Skin In Full-Thickness Wound Healing
生物打印皮肤在全层伤口愈合中的整合和重塑
- 批准号:
10063419 - 财政年份:2019
- 资助金额:
$ 5万 - 项目类别:
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