Tissue-Engineered Skin with Built-in Capillary Flow Newtworks

内置毛细管流动的组织工程皮肤 Newtworks

• 批准号: 7033232
• 负责人: HARIHARA BASKARAN
• 金额: $ 33.78万
• 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/7033232
• 关键词: capillary; clinical research; collagen; microfluidics; respiratory reflex; skin; tissue engineering; tissues

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）产品具有彻底改变医疗保健的潜力。人体中的许多组织和器官如软骨、骨、心脏瓣膜、血管、皮肤和肝脏正在被研究作为组织工程的目标。然而，其中只有少数如TE皮肤目前在临床上使用。此外，几乎所有目前正在使用或正在进行临床试验的TE产品都是针对无血管组织（例如心脏瓣膜和心血管拉格），或者在临床使用前没有血管化（例如皮肤替代品）。TE工程应用于更高功能的靶组织的主要障碍是缺乏开发具有用于对流递送营养物和去除代谢废物的集成微血管系统的TE产品的通用方法。我们的战略目标就是制定这样一种方法。在这个建议中，我们描述了一种方法来建立'血管化' TE皮肤结构。我们提出了四个具体的目标，解决了几个具体的问题，范围从组织的质量传递要求的制造，并在体外测试的组织与内置的毛细管流动网络。具体目标1。使用微加工和微流体方法评估细胞的传质要求。这将导致随后的毛细管流动网络的合理设计，并更好地理解组织结构中的传质限制。具体目标2。在生物聚合物基质中设计和制造最佳的平面微血管模拟系统。在这一特定目标中，为满足靶组织的代谢需求而定制的最佳毛细血管网络设计将嵌入胶原-糖胺聚糖（胶原-GAG）中，以使用微制造方法形成用于微血管的支架。具体目标3。通过内皮化和微流体技术使毛细血管网络“血管化”，并在体外对其进行评估。这将导致具有“微血管”网络的胶原蛋白-GAG支架，其可以通过对流方式提供营养并去除废物。具体目标4。在灌注生物反应器中开发复合TE皮肤，并评估集成对流运输系统对复合TE皮肤生长和分化的功效。在这一特定目标中，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，以测试基质的对流运输提高分化表皮形成速率的假设。这些目标的成功完成将产生可扩展的并且可以容易地在体内测试的产品。