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:10389894
- 负责人:
- 金额:$ 3.42万
- 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 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAlginatesAmericanAntioxidantsArtificial Endocrine PancreasAutoimmune DiseasesBeta CellBilirubinBiocompatible MaterialsBiomimeticsBloodBlood GlucoseCell DeathCell SeparationCell SurvivalCellsCessation of lifeChronicCoculture TechniquesDetectionDiabetes MellitusDiabetic mouseDimethyl SulfoxideDiseaseEncapsulatedEngineeringFaceGlucoseGoalsGraft RejectionHealthHousingHumanHydrogelsHyperglycemiaHypoxiaImmuneImmune responseImmune systemImmunosuppressive AgentsIn VitroInfectionInfiltrationInjectionsInjuryInsulinInsulin-Dependent Diabetes MellitusIslet CellIslets of LangerhansIslets of Langerhans TransplantationLabelLeadMalignant - descriptorManualsMediatingMethodsMicrocapsules drug delivery systemMicroencapsulationsMicrofluidicsMonitorMorbidity - disease rateMusNutrientOperative Surgical ProceduresOrganOrganoidsOvarian FolliclePancreasPancreas TransplantationPatientsPeriodicityPhysiologicalProceduresProductionQuality of lifeResearchRestRiskSamplingSolubilitySorting - Cell MovementStromal CellsStructureSystemT-LymphocyteTestingTimeTransplantationWaterbasecapsuleclinical translationcompliance behaviordeep learningdesigndetection methoddiabetic patienteffective therapyimplantationimprovedin 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.
项目摘要
据估计,目前有160万美国人患有1型糖尿病。的最常见方法
治疗1型糖尿病是通过每日血液监测和胰岛素注射,这可能会影响生活质量
并可能导致严重的健康问题。全胰腺移植是一种更持久的治疗选择
但涉及可导致并发症的侵入性手术,具有高发病率,
终生服用免疫抑制剂,这对健康非常有害。的一种方法
已经成为有希望的选择和许多研究焦点的糖尿病治疗是胰岛移植,
这是一种侵入性小得多的方法,但仍然需要患者服用免疫抑制剂,
移植排斥反应防止移植后需要免疫抑制剂的一种方法是通过
将胰岛包封在生物材料中,该生物材料可以允许营养交换,同时通过以下方式减轻免疫排斥:
防止免疫细胞浸润。微囊化胰岛移植仍面临免疫等诸多问题
反应和移植后胰岛活力差,这可以使用工程和
生物材料在这个项目中提出。目标1将集中于开发新的微胶囊化方法,
我们假设这将导致较低的胰岛细胞死亡和较低的移植后免疫反应,
vivo.胰岛的微流体包封提供了对微胶囊组成和配置的更大控制
其他封装方法。使用这种方法,仿生封装,模仿的结构,
胰腺和使用核壳设计的材料。实现无标签深度
学习检测方法,从芯片上的空胶囊中选择性地挑选装载胰岛的微胶囊,
用于移植的高纯度载胰岛微囊样品,可以大大提高效率,
与使用繁琐的手动分选方法相比,最大限度地减少污染(和相关的免疫反应)
在过去的日子里此外,胰岛将与胰腺基质细胞共包封,以产生仿生的
微环境(即,胰腺类器官)。微囊化的胰岛将被严格表征,
通过监测小鼠的血糖水平在糖尿病小鼠模型中进行体外和体内测试。目标2将
专注于开发基于纳米颗粒的策略,以进一步提高微胶囊的存活率
小岛生理量的抗氧化剂显示移植后胰岛存活率提高。封装
纳米颗粒中的抗氧化剂可以改善摄取并允许在胰岛移植期间持续释放。
将在体外测试负载抗氧化剂的纳米颗粒对胰岛存活和胰岛素产生的影响,
然后在体内测试它们对血糖水平的影响。通过结合深度学习,
选择性提取、核-壳水凝胶微囊化和纳米颗粒介质和抗氧化剂递送,
可以解决胰岛移植所面临的主要挑战。这种新颖的多尺度工程策略
具有广泛用于治疗1型糖尿病的临床转化的巨大潜力。
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 }}
Alisa White其他文献
Alisa White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('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:
10592297 - 财政年份:2022
- 资助金额:
$ 3.42万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 3.42万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 3.42万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 3.42万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 3.42万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 3.42万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 3.42万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 3.42万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 3.42万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 3.42万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 3.42万 - 项目类别:
Grant-in-Aid for Early-Career Scientists