Bioreactor Based Bone Tissue Engineering

一个多学科项目是开发用于骨组织工程的新型聚合物和聚合物陶瓷基质。利用化学、机械和材料工程以及细胞和分子生物学的原理，目标是创造和研究为新骨形成提供适当环境的结构替代物。这类基质的发展与新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基质系统中运输对细胞反应的影响提供了机会。此外，这些基质可以在临床应用于骨不连、手术关节、颅面缺损、假体植入物和/或植入物涂层的移植。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，这些三维基质已被证明支持体外成骨细胞的生长和成熟，并支持体内骨的形成。在计划的项目中，这些系统将进一步发展，并通过执行创新实验来优化这些系统，旨在利用三维矩阵来理解和增强骨形成。通过放置在动态细胞培养环境中，基质将暴露于流体和营养物质的流动中。研究人员假设，在运输增强的条件下，骨形成的质量最终将在这种基质系统中得到提高。此外，对细胞与这些可降解聚合物基质相互作用的方式的更基本的理解是需要寻求的。因此，研究人员建议评估植入这些仿生装置的成骨细胞的细胞表面受体表达。最后，将进行体内研究，检验这些组织工程生物反应器培养基质治疗骨不愈合缺陷的能力。将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形态学。在四年的时间框架内进行的研究应该产生重要的新的基础信息，广泛适用于组织工程。计划中的研究建立在由PI在先前资助的NSF研究中开发的聚合物微球的3-D聚合物支架的基础上。一个成功的项目的主要直接收益将是每年有近100万患者需要进行某种形式的骨移植手术。目前对于支架的优化设计参数，如机械强度、孔隙体积、孔径大小、降解率等还没有达成共识。所有这些问题都将在项目中解决。

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.