Tissue-Engineered Skin:Built-in Capillary Flow Networks

组织工程皮肤：内置毛细管流动网络

• 批准号: 7178512
• 负责人: HARIHARA BASKARAN
• 金额: $ 35.19万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7178512
• 关键词: Tissue; Engineered; Skin; Built; Capillary

DESCRIPTION (provided by applicant): 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 higher function is the lack of a general approach to develop TE products with inte- grated microvascular system for convective delivery of nutrients and removal of metabolic waste products. Our strategic goal is to develop such an approach. In this proposal, we describe a method to build 'vascularized' TE skin constructs. 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.

描述（由申请人提供）：组织工程（TE）产品有可能改变医疗保健。人体中的许多组织和器官，例如软骨，骨骼，心脏瓣膜，血管，皮肤和肝脏，正在研究作为Tis-Sue Engineering的靶标。但是，目前只有少数诸如TE皮肤之类的临床用途。此外，几乎所有目前正在使用或正在进行临床试验的TE产品均针对血管组织（例如心脏瓣膜和肺泡），或者在诊所使用之前未进行血管（例如，皮肤替代品）。将TE工程应用于较高功能的组织的主要障碍是缺乏开发具有整体微血管系统的TE产品的一般方法，用于对流养分和去除代谢废物。我们的战略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”皮肤结构的方法。我们提出了四个特定的目标，该目标解决了几个特定问题，这些问题从组织的传质需求到制造，以及通过内置毛细管流网络对组织进行体外测试。这些是：特定目的1。使用微生物和微流体方法来评估细胞的传质要求。这将导致随后的毛细血管流网络的合理设计，并更好地理解组织构建体中的传质限制。特定目的2。在生物聚合矩阵中设计和制造最佳的平面微血管模拟系统。在这个具体目的中，量身定制的最佳毛细管网络设计以满足靶组织的代谢需求，将嵌入胶原 - 糖糖胺聚糖（胶原蛋白-GAG）中，以使用微生物制作方法形成微囊菌的支架。特定的目的3。通过内皮化和微流体学“血管化”毛细血管网络，并在体外评估它们。这将导致具有“微血管”网络的胶原蛋白脚手架，可以通过对流手段供应营养并去除废物产品。具体目的4。在灌注生物反应器中发展复合材料皮肤，并评估对流传输系统对复合材料TE皮肤的生长和分化的功效。在这个具体目的中，将在灌注生物反应器中开发具有集成流动网络的复合皮肤替代物，以检验以下假设，即底物的对流运输可提高分化表皮的形成速率。这些目标的成功完成将导致可扩展的产品，并且可以在体内容易测试。