Tissue-Engineered Skin with Built-in Capillary Flow Newtworks

内置毛细管流动的组织工程皮肤 Newtworks

基本信息

批准号：
7568775
负责人：
HARIHARA BASKARAN
金额：
$ 33.84万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-15 至 2010-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7568775
关键词：
Address Angiogenic Factor Animals Biocompatible Materials Biological Models Biological Sciences Biomaterials Research Biomedical Research Bioreactors Blood Vessels Blood capillaries Cartilage Cell Culture Techniques Cells Clinic Clinical Clinical Trials Collagen Controlled Study Dermal Differentiation and Growth Engineering Environment Epidermis Excision Extracellular Matrix Proteins Gel Glycosaminoglycans Goals Healthcare Heart Valves Human Human body In Vitro Individual Knowledge Lead Liver Measures Metabolic Methodology Methods Microfabrication Microfluidics Nutrient Organ Perfusion Play Property Qualifying Research Research Personnel Research Proposals Role Skin Skin Substitutes Stratification Surface System Technical Expertise Techniques Testing Tissue Embedding Tissue Engineering Tissue Model Tissues Waste Products Work analog base bone capillary cell type design feeding graft function implantation improved in vitro testing in vivo insight keratinocyte meetings microsystems neovascularization next generation prevent programs repaired scaffold skin disorder success tissue support frame uptake

项目摘要

Tissue engineered (TE) products have the potential to revolutionize health care. A number of tissues and organs in the human body such as cartilage, bones, heart valves, blood vessels, skin and liver are being investigated as targets for tis- sue engineering. However, only a handful of them such as TE skin are currently in clinical use. In addition, almost all TE products currently in use or undergoing clinical trials are targeted at avascular tissues (e.g. heart valves and carti- lage), or are not vascularized before their use in the clinics (e.g. skin substitutes). A major obstacle in the application of TE engineering to target tissues of higherfunction is the lack of a general approach to develop TEproducts with inte- grated microvascular systemfor convective delivery of nutrients and removal of metabolic waste products. Our strate- gic goal is to develop such an approach. In this proposal, we describe a method to build 'vascularized' TE skin con- structs. We propose four specific aims, which address several specific issues that range from mass transfer requirements of tissues to fabrication, and in vitro testing of tissues with built-in capillary flow networks. These are: Specific Aim 1. To assess mass transfer requirements of cells, using microfabrication and microfluidic methodologies. This will lead to subsequent rational design of the capillary flow networks and to better understanding of mass transfer limita- tions in tissue constructs. Specific Aim 2. To design and fabricate optimal planar microvascular analog systems in biopolymeric matrices. In this specific aim, optimal capillary networks designs tailored to meet the metabolic demand of target tissue will be embedded in collagen-glycosaminoglycans (collagen-GAG) to form scaffolds for microvascula- ture using microfabrication methodologies. Specific Aim 3. To 'vascularize' capillary networks by endothelializa- tion and by microfluidics, and to assess them in vitro. This will lead to collagen-GAG scaffolds with 'microvascular' networks that can supply nutrients and remove waste products via convective means. Specific Aim 4. To develop composite TE skin in a perfusion bioreactor and to assess the efficacy of an integrated convective transport sys- tem on the growth and differentiation of composite TE skin. In this specific aim, composite skin substitutes with integrated flow networks will be developed in a perfusion bioreactor to test the hypothesis that convective transport of substrate improves the rate of formation of a differentiated epidermis. Successful completion of these aims will result in a product that is scalable and that can readily be tested in vivo.

组织工程（TE）产品有可能改变医疗保健。许多组织和器官正在研究人体，例如软骨，骨骼，心脏瓣膜，血管，皮肤和肝脏苏工程。但是，目前只有少数诸如TE皮肤之类的临床用途。另外，几乎所有目前正在使用或正在进行临床试验的TE产品针对的是血管组织（例如，心脏瓣膜和Carti- lage），或在诊所使用之前未被血管化（例如皮肤替代品）。应用的主要障碍针对更高功能的组织的工程是缺乏开发具有inte- 磨碎的微血管系统，可对流提供营养和代谢废物的去除。我们的策略 - GIC的目标是开发这种方法。在此提案中，我们描述了一种建立“血管化”皮肤的方法结构。我们提出了四个特定目标，该目标解决了从传质要求范围的几个特定问题与内置毛细管流网络的组织进行组织的组织和体外测试。这些是：特定目标1。使用微作用和微流体方法来评估细胞的传质需求。这会导致随后的毛细血管流网络的合理设计，并更好地了解传质限制组织构建体中的水平。特定目的2。在设计和制造最佳平面微血管模拟系统生物聚合矩阵。在这个特定目标中，最佳毛细管网络设计为满足代谢需求而量身定制靶组织的胶原蛋白糖胺聚糖（胶原蛋白 - gag）将嵌入到微卵管菌中的支架中使用微生物方法学方法。特定目的3。通过内皮层“血管化”毛细管网络 - 通过微流体和微流体，并在体外评估它们。这将导致带有“微血管”的胶原蛋白-GAG支架可以提供营养并通过对流手段去除废物产品的网络。特定目标4。发展在灌注生物反应器中复合皮肤，并评估对流传输系统的效力关于复合材料皮肤的生长和分化。在这个特定目的中，复合皮肤替代品集成流网络将在灌注生物反应器中开发，以检验以下假设底物提高了分化表皮的形成速率。这些目标成功完成将导致可扩展且可以在体内进行测试的产品。