Optimization of Bioreactor Based Tissue Engineering of Bone

Laurencin05503207该项目采用多学科方法开发骨组织工程旋转生物反应器中的新型聚合物基质。这种基质与新的组织培养技术相结合的发展为研究基于基质的系统中聚合物-细胞相互作用、聚合物基质对细胞反应的影响以及运输对细胞反应的影响提供了机会。第一个项目的目的是探索在旋转生物反应器中通过烧结微球形成适合骨组织工程的基质来构建新的聚合物结构。第二个目标是优化旋转生物反应器中的支架和操作环境，以及优化这些新型微球支架周围的支架组成、支架的孔径大小、旋转生物反应器的转速和细胞种植密度等物理化学参数。第三个目标是在生物反应器中研究生长因子的传递，通过在基质中加入可能促进细胞内皮化和骨生长的因子来建立之前的工作。在第四个目标中，将进行广泛的体内研究，测试这些组织工程化生物反应器培养基质修复临界大小骨缺损的能力。这些研究将密切关注愈合缺损的机械强度以及缺损处的组织学和组织形态计量学。这些研究应该会产生在组织工程中广泛适用的重要的新的基本信息。在教育方面，这项研究预计将对本科和研究生阶段未被充分代表的少数民族学生的培训产生特殊影响，因此将极大地丰富我国可用的科学资源水平。

Laurencin05503207The project employs a multidisciplinary approach towards the development of novel polymer based matrices in rotating bioreactors for bone tissue engineering. 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. The first project aim is to explore the development of new polymer constructs fabricated by sintering microspheres to form matrices suitable for bone tissue engineering in rotating bioreactors. In the second aim, the scaffolds and operating environment is to be optimized in rotating bioreactors as well as the optimizing of physicochemical parameters such as scaffold composition, pore size of scaffolds, rotating speed of rotating bioreactors and cell seeding density surrounding these novel microsphere- based scaffolds. The third aim, the delivery of growth factors, will be studied in the bioreactors, building on the previous work via incorporating factors into the matrix that may enhance cellular endothelialization and bone growth. And, in the fourth aim, extensive in vivo studies will be performed, examining the ability of these tissue engineered bioreactor cultured matrices to heal critical size bone defects. These studies will pay careful attention to the mechanical strength of the healing defect and the histology and histomorphometry at the defect site. The studies should yield important new fundamental information broadly applicable in tissue engineering. Educationally, the research is expected to have a special impact on the training of underrepresented minority students at the undergraduate and graduate levels, and hence would greatly enrich the level of scientific resources available to our nation.Gilbert B. DeveyApril 7, 2005