Shear Flow--Osteoinductive Stimulus for bone Engineering

剪切流--骨工程的骨诱导刺激

• 批准号: 6793803
• 负责人: Aaron Sanford Goldstein
• 金额: $ 7.5万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6793803
• 关键词: biological transport; biotechnology; bone development; bone marrow; cell adhesion; cell differentiation; cell growth regulation; cell type; fibronectins; intermolecular interaction; laboratory rat; osteoblasts; polymerase chain reaction; statistics /biometry; stem cell factor; stem cell transplantation; stem cells; tissue /cell culture; tissue engineering; tissue support frame

Bone marrow stromal stem cells (BMSCs) are multipotent progenitor cells that have great potential as an osteoinductive and osteogenic component for engineered bone tissue. Incorporation of these cells into clinically effective graft materials relies on the establishment of in vitro culture techniques that can direct expansion and preferential differentiation into the osteoblastic lineage. Successful techniques would lead to the creation of a bone-like tissue replete with osteoconductive and osteoinductive factors to stimulate host integration and remodeling. Building on our evidence that BMSCs are mechanosensitive and that flow stimulates phenotypic markers of osteoblastic maturation, we seek to understand how flow modulates phenotypic markers. The specific aims of this project involve systematic evaluation of three complementary components of a perfusion strategy. 1) Characterize the effect of shear stress magnitude and mass transport rate on expression of phenotypic markers of osteoblastic differentiation. 2) Assess the impact of intermittent flow strategies on osteoblastic differentiation. 3) Characterize the effect of adhesive ligand activity on differentiation and probe for synergy with shearing flow. The proposed studies - involving osteoprogenitor cells suitable for bone tissue engineering applications -will be performed under well-characterized conditions in a parallel-plate flow chamber to identify osteoinductive transport effects of perfusion, establish benchmarks of osteoblastic differentiation, and determine effective culture strategies. These findings will be used to predict optimal culture conditions for osteoblastic differentiation of BMSCs within perfused 3D scaffold geometries, with the goal of producing engineered bone tissues suitable for clinical testing.

骨髓基质干细胞（BMSCs）是一种多能性祖细胞，在工程化骨组织中具有很大的成骨诱导潜能。将这些细胞掺入临床有效的移植材料依赖于体外培养技术的建立，该技术可以直接扩增并优先分化成成骨细胞谱系。成功的技术将导致产生充满骨传导和骨诱导因子的骨样组织，以刺激宿主整合和重塑。基于我们的证据，即BMSCs是机械敏感的， 刺激成骨细胞成熟的表型标志物，我们试图了解流动如何调节表型标志物。该项目的具体目标包括系统评价灌注策略的三个互补组成部分。 1)表征剪切应力大小和质量传递速率对成骨细胞分化表型标志物表达的影响。 2)评估间歇性血流策略对成骨细胞分化的影响。 3)表征粘附配体活性对分化的影响，并探测与剪切流的协同作用。 拟议的研究-涉及适用于骨组织工程应用的骨祖细胞-将在平行板流动室中在充分表征的条件下进行，以确定灌注的骨诱导运输效应，建立成骨细胞分化的基准，并确定有效的培养策略。这些发现将用于预测灌注3D支架几何形状内BMSC成骨分化的最佳培养条件，目的是生产适合临床测试的工程化骨组织。