Bioreactor Based Bone Tissue Engineering

基于生物反应器的骨组织工程

• 批准号: 0343620
• 负责人: Cato Laurencin
• 金额: $ 53.54万
• 依托单位: University of Virginia Main Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-15 至 2005-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0343620&HistoricalAwards=false
• 关键词: Bioreactor; Based; Bone; Tissue; Engineering

A multidisciplinary project is to develop novel polymer and polymer-ceramic based matrices for bone tissue engineering. Using principles from chemical, mechanical, and materials engineering as well as cell and molecular biology, the goal is to create and study structural replacements that provide an environment appropriate for new bone formation. The development of a matrix of this sort combined with novel tissue culture technology provides opportunities for studying polymer-cell interactions, polymer matrix effects on cellular response, and effects of transport on cellular response in matrix based systems. Moreover these matrices may find clinical applications in grafting of non-unions, surgical arthrodeses, cranio-facial defects, and prosthetic implants and/or implant coatings. The researchers recently described the development of novel degradable microsphere-based matrices for bone tissue engineering. In preliminary studies these three-dimensional matrices have been shown to support the growth and maturation of osteoblast cells in vitro, and support the formation of bone in vivo. In the panned project these systems would be developed further and optimized these systems by performing innovative experiments aimed at understanding and enhancing bone formation using three dimensional matrices. The matrix would be exposed to fluid and nutrient flux via placement in a dynamic cell culturing environment. The researchers have hypothesized that in conditions where transport is enhanced, the quality of bone formation will ultimately be enhanced in such matrix systems. Additionally, a more fundamental understanding of the manner in which cells interact with these degradable polymeric matrices is to be sought. Therefore studies are proposed to evaluate cell surface receptor expression of osteoblasts seeded onto these biomimetic devices. Finally, in vivo studies will be performed, examining the ability of these tissue engineered bioreactor cultured matrices to heal non-union bone defects. Careful attention will be given to the mechanical strength of the healing defect and the short- and long-term histology and histomorphometry at the defect site. The studies to be performed in a four year time-frame should yield important new fundamental information broadly applicable in tissue engineering.The planned investigation builds on the foundation of 3-D polymer scaffolds from polymer microspheres developed by the PI in previously funded NSF studies.The major direct benefit from a successful project would be the nearly 1 million patients each year who have surgeries that require some form of bone grafting. Presently there is no consensus on the optimized scaffold design parameters, e.g. mechanical strength, pore volume, pore size, and degradation rate. All of these issues are to be addressed in the project.

一个多学科的项目是开发用于骨组织工程的新型聚合物和聚合物 - 陶瓷矩阵。使用化学，机械和材料工程以及细胞和分子生物学的原理，其目标是创建和研究结构替代品，以提供适合新骨形成的环境。这种基质的发展与新型的组织培养技术相结合，为研究聚合物细胞相互作用，聚合物基质对细胞反应的影响以及转运对基于基于基质的系统中细胞反应的影响提供了机会。此外，这些矩阵可能会在非工会，手术关节炎，颅面缺陷以及假体植入物和/或植入物涂料方面发现临床应用。研究人员最近描述了用于骨组织工程的新型可降解微球基质的发展。在初步研究中，这些三维矩阵已被证明可以在体外支持成骨细胞的生长和成熟，并支持体内骨骼的形成。在削减项目中，这些系统将进一步开发，并通过进行旨在使用三维矩阵来理解和增强骨形成的创新实验来优化这些系统。在动态细胞培养环境中，基质将通过放置在液体和营养通量中暴露于液体和营养通量。研究人员假设，在增强运输的条件下，在此类基质系统中最终将提高骨形成的质量。此外，要寻求对细胞与这些可降解聚合物矩阵相互作用的方式的更基本的理解。因此，提出了研究来评估骨细胞的细胞表面受体表达，这些细胞细胞播种在这些仿生装置上。最后，将进行体内研究，检查这些组织工程生物反应器培养的基质治愈非工会骨缺损的能力。仔细注意愈合缺陷的机械强度以及缺陷部位的短期和长期组织学和组织学和组织形态计量学。这些研究应在四年的时间范围内进行，应产生重要的新基本信息，广泛适用于组织工程。计划进行的研究建立在PI由PI在先前资助的NSF研究中开发的3-D聚合物支架的基础。目前，在优化的脚手架设计参数上尚无共识，例如机械强度，孔体积，孔径和降解速率。所有这些问题都将在项目中解决。