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首页> 外文学位 >Bioreactor-based bone tissue engineering using poly(lactic-co-glycolic acid)/nano-hydroxyapatite composite scaffolds and bone marrow mesenchymal stem cells.
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Bioreactor-based bone tissue engineering using poly(lactic-co-glycolic acid)/nano-hydroxyapatite composite scaffolds and bone marrow mesenchymal stem cells.

机译：基于生物反应器的骨组织工程，使用聚乳酸-乙醇酸/纳米羟基磷灰石复合支架和骨髓间充质干细胞。

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摘要

One concern in bone tissue engineering is the limited bone ingrowth into scaffolds due to inadequate diffusion of oxygen, nutrients, and waste when cell loaded scaffolds are cultured statically. To overcome limitations associated with static culture, a dynamic culture system using the High Aspect Ratio Vessel (HARV) bioreactor was adopted by our laboratory for bone tissue engineering applications.;This dissertation presented the design, development, and characterization of buoyant poly (lactic-co-glycolic acid) (PLAGA)/nano-hydroxyapatite (n-HA) composite scaffolds for bone tissue engineering applications in HARV bioreactors. Composite microspheres with various PLAGA/n-HA ratios were synthesized and characterized. The 3-dimensional (3D) scaffolds were fabricated via a sintered microsphere method. Mechanical properties of the scaffolds were found to be modulated by sintering conditions and PLAGA/n-HA ratio. After optimization, PLAGA/n-HA (4:1) scaffolds sintered at 90°C for 3 hours exhibited the highest mechanical properties, which were higher than those of pure polymeric scaffolds. The newly developed scaffolds exhibited desirable pore structure and density for applications in HARV bioreactor based bone tissue engineering. The incorporation of n-HA imparted bioactivity to the scaffolds and affected the degradation of scaffolds in aqueous media. The PLAGA/n-HA scaffolds were found to be cytocompatible using both rabbit mesenchymal stem cells (RMSCs) and human mesenchymal stem cells (HMSCs). During in vitro static culture, PLAGA/n-HA scaffolds supported MSC proliferation, phenotypic expression, and calcium deposition into matrix. Finally, the newly developed composite scaffolds were applied in the dynamic culture environment in HARV bioreactors and the cellular behavior of HMSCs was investigated. HMSCs were found to distribute throughout the 3D structure of PLAGA/n-HA scaffolds and exhibited elevated proliferation, differentiation and mineralization on PLAGA/n-HA scaffolds than on PLAGA scaffolds.;The work described in this dissertation presented the successful development of PLAGA/n-HA composite scaffolds with superior physical and biological properties and provided strong evidence on their efficiency in generating cell/scaffold constructs with uniform cell and ECM distribution throughout the 3D structure when cultured with MSCs in HARV bioreactors. This tissue engineering strategy which utilizes PLAGA/n-HA scaffolds with MSCs in HARV bioreactors is promising in generating "engineered" tissue for potential therapeutic applications.
机译：骨组织工程学中的一个问题是，当静态加载细胞加载的支架时，由于氧气，营养物质和废物的扩散不充分，导致骨骼向支架内的生长受限。为了克服与静态培养相关的局限性，我们的实验室采用了采用高长宽比容器（HARV）生物反应器的动态培养系统来进行骨组织工程应用。本论文介绍了浮力聚乳酸（乳酸菌）的设计，开发和表征（乙醇酸）（PLAGA）/纳米羟基磷灰石（n-HA）复合支架，用于HARV生物反应器中的骨组织工程应用。合成并表征了具有不同PLAGA / n-HA比的复合微球。通过烧结微球法制造3维（3D）支架。发现该支架的机械性能受烧结条件和PLAGA / n-HA比的调节。经过优化后，在90°C下烧结3小时的PLAGA / n-HA（4：1）支架表现出最高的机械性能，高于纯聚合物支架的机械性能。新开发的支架展示出理想的孔结构和密度，可用于基于HARV生物反应器的骨组织工程。 n-HA的掺入赋予了支架生物活性并影响了支架在水性介质中的降解。使用兔间充质干细胞（RMSC）和人间充质干细胞（HMSC），发现PLAGA / n-HA支架具有细胞相容性。在体外静态培养过程中，PLAGA / n-HA支架支持MSC增殖，表型表达和钙沉积到基质中。最后，将新开发的复合支架材料应用于HARV生物反应器的动态培养环境，研究了HMSCs的细胞行为。发现HMSCs分布在PLAGA / n-HA支架的整个3D结构中，并且在PLAGA / n-HA支架上的增殖，分化和矿化作用比PLAGA支架高。;本论文中的工作表明PLAGA / n-HA支架的成功开发n-HA复合支架具有优异的物理和生物学特性，并提供了有力的证据证明当与MSCs在HARV生物反应器中培养时，它们在生成在3D结构中具有均匀的细胞和ECM分布的细胞/支架结构的效率。这种在HARV生物反应器中利用PLAGA / n-HA支架和MSC的组织工程策略有望在产生“工程化”的组织以用于潜在的治疗应用中。

著录项

  • 作者

    Lv, Qing.;

  • 作者单位

    University of Virginia.;

  • 授予单位 University of Virginia.;
  • 学科 Engineering Chemical.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 207 p.
  • 总页数 207
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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