Development of Bioactive Oxygen Platforms for Extrahepatic Islet Transplantation

肝外胰岛移植生物活性氧平台的开发

基本信息

批准号：
8606657
负责人：
MARIA MARGARITA CORONEL
金额：
$ 3.4万
依托单位：
UNIVERSITY OF MIAMI CORAL GABLES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-15 至 2014-08-25
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8606657
关键词：
Address Angiogenic Factor Belief Beta Cell Binding Biocompatible Materials Blood Vessels Cell Death Cell Line Cell Survival Cell Therapy Cell physiology Cells Cessation of life Computer Simulation Development Diabetes Mellitus Digestive System Disorders Encapsulated Engineering Engraftment Ensure Environment Equipment Extrahepatic Gene Expression Generations Geometry Growth Factor Hydrogels Hypoxia Hypoxia Inducible Factor Implant In Vitro Incidence Institutes Insulin-Dependent Diabetes Mellitus Islets of Langerhans Islets of Langerhans Transplantation Kidney Diseases Kinetics Life Expectancy Mission Modeling Monitor National Institute of Biomedical Imaging and Bioengineering Nutrient Oxygen Patients Peroxides Physics Physiological Polymers Population Production Protein Engineering Public Health Quality of life Research Rodent Model Silicones Site Solid Staging Structure System Techniques Testing Time Tissue Engineering Tissues Translating Transplantation Vascularization Work angiogenesis base blood glucose regulation clinically relevant design diabetic graft function implantation improved in vivo islet neovascularization prevent protein expression prototype public health relevance repaired scaffold success treatment site vascular bed wound

项目摘要

DESCRIPTION (provided by applicant): A major hindrance for the successful transplantation of tissue-engineered constructs is proper oxygenation in the early period post-transplantation prior to the establishment of a functioning vascular bed. Thus, this proposal is concerned with the development of oxygen-generating biomaterials to enhance nutrient delivery in tissue-engineered constructs upon implantation. Our working hypothesis is that by introducing an oxygen generating biomaterial, in conjunction with the sustained and local delivery of pro-angiogenic factors, we can prevent hypoxia-induced cellular death during the early engraftment period. In this proposal we seek to overcome hypoxia-induced cellular death by delivering localized supplemental oxygen to our cell-based constructs, and, at the same time, decreasing the time for revascularization via the introduction of pro- angiogenic matrices. The specific aims of this proposal are: 1) to develop and characterize a prototype of an oxygen generating biomaterial that has the capacity to provide a sufficient amount of oxygen to beta cells and prevents hypoxia-induced cellular death; and 2) to introduce a pro-angiogenic releasing hydrogel that, in the presence of the oxygen generating biomaterial, enhances the formation of a vascular network for long-term graft function. The oxygen production from the biomaterial will be assessed via non-invasive oxygen monitoring. The viability, functionality, protein and gene expressions of the cell-based constructs will be assessed both in vitro, with beta cells and islets and in vivo in a chemically induced diabetic rodent model. It is our belief that by improving the overall oxygen delivery to the implant, both through oxygen generating material and promotion of vascularization, we have the potential to substantially improve construct engraftment and long term success of cellular based therapies for the treatment of type I diabetes mellitus (TIDM).

描述（由申请人提供）：成功移植组织工程构建体的主要障碍是在建立功能正常的血管床之前的早期移植后期的适当氧合。因此，该建议与生成氧生物材料的发展有关，以增强植入后组织工程结构中的营养递送。我们的工作假设是，通过引入产生生物材料的氧气，结合促促血管生成因子的持续和局部递送，我们可以防止在植入早期植入期间缺氧引起的细胞死亡。在该提案中，我们试图通过向基于细胞的构建体传递局部补充氧来克服缺氧诱导的细胞死亡，同时通过引入促血管生成基质来减少血运重建的时间。该提案的具体目的是：1）开发和表征产生生物材料的原型，该原型具有为β细胞提供足够量的氧气并防止缺氧诱导的细胞死亡的能力； 2）引入促血管生成释放水凝胶，该水凝胶在存在生物材料的氧气的情况下增强了用于长期移植功能的血管网络的形成。生物材料产生的氧气将通过非侵入性氧监测评估。在化学诱导的糖尿病啮齿动物模型中，将在体外评估基于细胞构建体的生存力，功能，蛋白质和基因表达。我们相信，通过通过氧气产生材料和促进血管形成的植入物的总体氧气递送，我们有可能实质上改善构建体的植入和基于细胞的疗法的长期成功，以治疗I型糖尿病型糖尿病（TIDM）。