INDIVIDUAL PREDOCTORAL DENTAL SCIENTIST FELLOWSHIP

组织工程领域的发展是由于需要器官/组织替换的患者的器官和组织供应不足。器官和组织移植的一个有吸引力的替代方案可以极大地扩大临床医生治疗需要新器官和组织的患者的能力，那就是选择性地移植合适的细胞类型(S)。将细胞群移植到可生物降解的聚合物基质上，以便从这些移植的细胞中设计出功能组织块是一个有趣的策略。然而，这些细胞的存活依赖于营养物质和废物在基质上的移植细胞和周围宿主组织中存在的血管系统之间的扩散。目前，这种血管网络是使能够形成完整器官的大规模组织块工程化的限制因素。这项拟议的研究侧重于增加这些聚合物基质中的血管网络的策略，以便创造大量的骨组织，能够替代骨缺损。这项建议的具体目标是：目标1-确定使微血管内皮细胞产生生长因子/介质的策略，a)将诱导强烈和持续的血管生成反应，b)将从成骨前体诱导骨发育和生长。我们将首先关注介体Bc l-2，Angiopoietin(两种有效的血管生成诱导剂)和成骨介体BMP-2；目标2-将这些不同的内皮细胞群体整合到可生物降解的聚合物基质中，并测试它们在体外和体内形成毛细血管的单独和联合能力；目的3-确定骨祖细胞移植到可生物降解的基质上时的基线骨形成；目的4-确定特定目标1-3中确定的内皮细胞、骨祖细胞和基质的适当组合是否会导致体内(SCID小鼠模型)持续而有力的血管生成反应，能够支持骨祖细胞的骨发育。

The field of tissue engineering has developed due to the inadequate supply of organs and tissues for patients requiring organ/tissue replacement. An attractive alternative to organ and tissue transplantation that could immensely expand clinicians' ability to treat patients requiring new organs and tissues is the selective transplantation of the appropriate cell type(s). Transplanting cell populations on biodegradable polymer matrices in order to engineer a functional tissue mass from these transplanted cells is an intriguing strategy. However, the survival of these cells is dependent on diffusion of nutrients and waste products between the transplanted cells on the matrix and the vasculature existing in the surrounding host tissue. Currently, this vascular network is the limiting factor in allowing the engineering of large-scale masses of tissue capable of forming whole organs. The proposed research focuses on strategies to increase the vascular network within these polymer matrices in order to create significant amounts of bone tissue capable of replacing osseous defects. The specific aims of this proposal are: Aim 1-To define strategies to engineer microvascular endothelial cells to produce growth factors/mediators that a) will induce a vigorous and sustained angiogenic response, and b) will induce bone development and growth from osteogenic precursors. We will initially look at the mediators Bcl-2, angiopoietin (two potent inducers of angiogenesis), and the osteogenic mediator BMP-2; Aim 2- To incorporate these different endothelial cell populations into biodegradable polymer matrices and to test their individual and combined abilities to form capillaries in vitro and in vivo; Aim 3- To determine the baseline bone formation when osteo-progenitor cells are transplanted on a biodegradable matrix; Aim 4-To determine if an appropriate combination of endothelial cells, osteo-progenitor cells, and matrix, as determined in Specific Aims 1-3, will result in a sustained and vigorous angiogenic response in vivo (SCID mouse model) capable of supporting bone development from osteo-progenitor cells.