MECHANICALLY GUIDED TISSUE REGENERATION

描述 （摘自申请人摘要）本研究的目的是 检验一个整体假设，即组织的整合和功能 用于骨再生的工程化构建体受到以下因素的显著影响： 通过细胞外基质传递物理力。 利用一系列体内大鼠模型，研究人员将测试 器械介导的机械力和局部 在刺激修复和合并的生物因子的输送 组织工程骨替代物。 颅面模型和 长骨部位使用专门设计的外固定器， 实验控制机械加载的实现 通过手术创建的截骨间隙的条件。 局部生物因素 将通过在这些裂缝中放置DNA传递基质来产生 差距。 机械和生物因素对组织修复的影响 再生将通过记录基因的空间模式来分析 表达、基质合成和骨形态作为时间的函数， 解剖位置 这些信息对于制定战略以取代 或增加颅面或无骨骨骼中的骨缺损。 识别影响整合和重塑的因素 组织工程移植将显著改善， 更可靠的仿生疗法

DESCRIPTION (Adapted from the applicant's abstract) The purpose of this research is to test the global hypothesis that the incorporation and function of a tissue engineered construct for bone regeneration is significantly influenced by the transmission of physical forces through its extracellular matrix. Utilizing a series of in vivo rat models, the investigators will test for the synergistic affects of device mediated mechanical forces and local delivery of biologic factors in stimulating the repair and incorporation of tissue engineered bone substitutes. The models in both a cranial-facial and long bone site utilize specifically designed external fixators which enable the implementation of experimentally controlled mechanical loading conditions across surgically created osteotomy gaps. Local biologic factors will be produced by placing DNA-delivering matrices within these fracture gaps. The effects of the mechanical and biologic factors on tissue repair and regeneration will be assayed by documenting the spatial patterns of gene expression, matrix synthesis, and bone morphology as a function of time and anatomic location. This information is fundamental to the development of strategies to replace or augment bony defects in the cranial-facial or appendicular skeleton. Identification of factors which influences the incorporation and remodeling of tissue engineered transplants will lead to significantly improved and more reliable biomimetic therapies.