Fabrication, perfusion and imaging of pre-vascularized tissue scaffolds

描述（由申请人提供）：组织工程的一个重要障碍是供体组织的充分灌注。由于氧气的扩散极限小于200um (Carmeliet and Jain, 2000)，即使是相当简单的组织构建也需要在移植后快速灌注。因此，成功的工程组织仅限于薄的或血管组织，如皮肤、软骨、膀胱等（Rouwkema等，2008）。有趣的是，一个相关的问题困扰着治疗缺血性疾病的血管生成方法。尽管发现了许多促血管生成因子，但基于单一因素的临床治疗策略完全不成功（Henry et al., 2003; Molin and Post, 2007; Simons, 2005）；然而，生长因子的组合在促进稳定的血管生成和改善受损循环方面开始显示出巨大的希望，激发了新的促血管生成组织支架的设计。在这里，我们将在一种新的策略中使用多个转基因荧光报告系来优化用于组织工程和治疗缺血性疾病的水凝胶支架。研究目标包括优化水凝胶支架设计以输送生长因子和细胞，以及表征宿主反应以指导新的支架设计。

DESCRIPTION (provided by applicant): A significant hurdle in tissue engineering is adequate perfusion of donor tissue. Since the diffusion limit of oxygen is <200um (Carmeliet and Jain, 2000), even fairly simple tissue constructs require rapid perfusion following transplantation. Thus, successfully engineered tissues are restricted to thin or a vascular tissues such as skin, cartilage, bladder etc (Rouwkema et al., 2008). Interestingly, a related problem plagues therapeutic angiogenesis approaches to treat ischemic disease. Despite the discovery of numerous pro-angiogenic factors, clinical therapeutic strategies based on single factors have been wholly unsuccessful (Henry et al., 2003; Molin and Post, 2007; Simons, 2005); however, combinations of growth factors are beginning to show great promise in promoting stable angiogenesis and improving damaged circulation, inspiring new designs of pro-angiogenic tissue scaffolds. Here we will use multiple transgenic fluorescent reporter lines in a novel strategy to optimize hydrogel scaffolds for tissue engineering and for use in treating ischemic disease. Research goals include the optimization of hydrogel scaffold design to deliver growth factors and cells and the characterization of the host response to guide new scaffold designs. PUBLIC HEALTH RELEVANCE: Current strategies to repair damaged tissues are limited by the lack of efficient methods to improve circulation and rebuild tissues in damaged areas. In this proposal we will design and test whether custom engineered scaffolds can aid in vessel infiltration and can deliver donor cells that can participate in repair.