Deep Learning-reinforced Engineering of Pancreatic Organoids with Micro-nano Biomaterials for Type 1 Diabetes Treatment
利用微纳米生物材料深度学习强化胰腺类器官工程治疗 1 型糖尿病
基本信息
- 批准号:10592297
- 负责人:
- 金额:$ 2.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAlginatesAmericanAntioxidantsArtificial Endocrine PancreasAutoimmune DiseasesBeta CellBilirubinBiocompatible MaterialsBiomimeticsBloodBlood GlucoseCell AggregationCell DeathCell SeparationCell SurvivalCellsCessation of lifeChronicCoculture TechniquesDetectionDiabetes MellitusDiabetic mouseDimethyl SulfoxideDiseaseEncapsulatedEngineeringFaceGlucoseGoalsGraft RejectionHealthHousingHumanHydrogelsHyperglycemiaHypoxiaImmuneImmune responseImmune systemImmunosuppressive AgentsIn VitroInfectionInjectionsInjuryInsulinInsulin-Dependent Diabetes MellitusIslet CellIslets of LangerhansIslets of Langerhans TransplantationLabelLaboratoriesMalignant - descriptorManualsMediatingMethodsMicrocapsules drug delivery systemMicrofluidicsMonitorMorbidity - disease rateMusNutrientOperative Surgical ProceduresOrganOrganoidsOvarian FolliclePancreasPancreas TransplantationPatientsPeriodicalsPhysiologicalProceduresProductionQuality of lifeResearchRestRiskSamplingSolubilitySortingStromal CellsStructureSystemT-LymphocyteTestingTimeTransplantationWatercapsuleclinical translationcompliance behaviordeep learningdesigndetection methoddiabetic patienteffective therapyimmune cell infiltrateimplantationimprovedin vitro testingin vivoin vivo evaluationisletlearning strategymortalitymouse modelnanonanoparticlenanoparticle deliverynovelpost-transplantpreventstemuptake
项目摘要
PROJECT SUMMARY
An estimated 1.6 million Americans are currently living with type 1 diabetes. The most common method of
treating type 1 diabetes is through daily blood monitoring and insulin injections, which can affect quality of life
and may result in severe health issues. Full pancreatic transplantations are a more permanent treatment option
but involve invasive surgery that can lead to complications, has a high morbidity rate, and patients are required
to take immunosuppressants for the rest of their lives which can be very detrimental to health. One method for
diabetes treatment that has become a promising option and focus of a lot of research is islet transplantation,
which is a much less invasive method but still requires patients to take immunosuppressants or risk
transplantation rejection. A way to prevent the need for immunosuppressants post-transplantation is through
encapsulating the islets in biomaterials which can allow nutrient exchange while mitigating immune rejection by
preventing immune cell infiltration. Encapsulated islet transplantation still faces many problems including immune
responses and poor islet viability post-transplantation, which may be addressed using engineering and
biomaterials as proposed in this project. Aim 1 will focus on developing novel microencapsulation methods,
which we hypothesize will result in lower islet cell death and lower post-transplantation immune responses in
vivo. Microfluidic encapsulation of islets gives greater control over microcapsule composition and configuration
than other encapsulation methods. Using this method, a biomimetic encapsulation that mimics the structure of
the pancreas and uses materials in a core-and-shell design can be achieved. Implementing a label-free deep
learning detection method to selectively pick islet-laden microcapsules from empty capsules on-chip to obtain a
highly pure sample of islet-laden microcapsules for transplantation, may greatly improve the efficiency and
minimize contamination (and associated immune response), compared to tedious manual sorting methods used
in the past. Furthermore, the islets will be co-encapsulated with pancreatic stromal cells to create a biomimetic
microenvironment (i.e., pancreatic organoid). The microencapsulated islets will be rigorously characterized in
vitro and tested in vivo in a diabetic mouse model by monitoring blood glucose levels of the mice. Aim 2 will
focus on developing a nanoparticle-based strategy for further improving the survival of the microencapsulated
islets. Physiological amounts of antioxidants show enhanced islet survival post-transplantation. Encapsulating
antioxidants in nanoparticles can improve the uptake and allow for sustained release during islet transplantation.
Effect of the antioxidant-laden nanoparticles on islet survival and insulin production will be tested in vitro and
then their effects on blood glucose levels tested in vivo. Through a combination of deep learning-enabled
selective extraction, core-shell hydrogel microencapsulation, and nanoparticle-mediatexd antioxidants delivery,
major challenges facing islet transplantation may be addressed. This novel multiscale engineering strategy has
great potential for clinical translation to be widely used for treating type 1 diabetes.
项目总结
项目成果
期刊论文数量(0)
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Alisa White其他文献
Alisa White的其他文献
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{{ truncateString('Alisa White', 18)}}的其他基金
Deep Learning-reinforced Engineering of Pancreatic Organoids with Micro-nano Biomaterials for Type 1 Diabetes Treatment
利用微纳米生物材料深度学习强化胰腺类器官工程治疗 1 型糖尿病
- 批准号:
10389894 - 财政年份:2022
- 资助金额:
$ 2.39万 - 项目类别:
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