High-Modulus Polyurethanes for Bone Tissue Engineering

用于骨组织工程的高模量聚氨酯

• 批准号: 6970585
• 负责人: Aaron Sanford Goldstein
• 金额: $ 17.26万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6970585
• 关键词: bioengineering /biomedical engineering; biomaterial compatibility; biomaterial development /preparation; bone; bone marrow; cell differentiation; cell proliferation; chemical synthesis; laboratory rat; osteoblasts; perfusion; polyurethanes; stromal cells; tissue /cell culture; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): Ex vivo manufacture of clinically effective engineered bone requires the incorporation of bioactive factors into a biomaterial scaffold that will stimulate vascular infiltration, tissue integration and remodeling in vivo. Polyurethanes are a class of durable biocompatible polymers well suited for numerous biomedical applications. We hypothesize that we can use known structure-property relationships to synthesize a family of novel high modulus, degradable, biocompatible segmented polyurethanes that are capable of supporting bone tissue formation. Concurrently, bone marrow stromal cells (BMSCs) are a class of adult stem cells that readily form mature bone in vivo and can be directed ex vivo to differentiate and secrete a bone like extracellular matrix. We hypothesize that by culturing BMSCs in porous polyurethane scaffolds using novel perfusion strategies to deliver nutrients and oxygen and activate mechanotransductive pathways, we can direct osteoblastic maturation and synthesis of those bioactive factors necessary to stimulate healing in vivo. The goals of the project are: 1) Synthesize a family of high modulus (10-500 MPa) segmented polyurethanes from biocompatible and biologically-derived precursors. 2) Demonstrate biocompatibility, degradability and processibility of polyurethanes into high modulus (0.1 to 5 MPa) porous foam scaffolds. 3) Develop a bone-like tissue ex vivo and determine the effect of polyurethane scaffold modulus and perfusion regimen on ex vivo bone formation. The high-risk innovations of this project are 1) a family of degradable polyurethanes tuned for bone tissue engineering applications, 2) a methodology to process polyurethanes into high porosity, interconnected pore foams with high compressive modulus, and 3) a strategy of intermittent perfusion culture that enhances ex vivo bone tissue development. The results of this project will be a family of engineered bone tissues to be tested in vivo, and methodologies and strategies to construct the next generation of engineered bone tissue.

描述（由申请人提供）：临床有效的工程化骨的离体制造需要将生物活性因子掺入生物材料支架中，这将刺激体内血管浸润、组织整合和重塑。聚乙烯是一类耐用的生物相容性聚合物，非常适合于许多生物医学应用。我们假设，我们可以使用已知的结构-性能关系来合成一个新的高模量，可降解，生物相容性的分段聚氨酯，能够支持骨组织形成的家庭。同时，骨髓基质细胞（BMSC）是一类成体干细胞，其在体内容易形成成熟骨，并且可以离体定向分化并分泌骨样细胞外基质。我们假设，通过在多孔聚氨酯支架中培养BMSCs，使用新的灌注策略来提供营养和氧气并激活机械转导途径，我们可以指导成骨细胞成熟和合成刺激体内愈合所需的生物活性因子。该项目的目标是： 1)从生物相容性和生物衍生的前体合成一系列高模量（10-500 MPa）嵌段聚氨酯。 2)证明聚氨酯的生物相容性、可降解性和可加工性，使其成为高模量（0.1至5 MPa）多孔泡沫支架。 3)离体培养骨样组织，并确定聚氨酯支架模量和灌注方案对离体骨形成的影响。 该项目的高风险创新是1）一系列可降解聚氨酯，用于骨组织工程应用，2）将聚氨酯加工成具有高压缩模量的高孔隙率、互连孔泡沫的方法，以及3）增强离体骨组织发育的间歇灌注培养策略。该项目的结果将是一个家庭的工程化骨组织进行体内测试，方法和策略，以构建下一代工程化骨组织。