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Growth and remodeling in engineered soft tissue.

机译：在工程软组织中的生长和重塑。

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摘要

Left to their own devices, tendons and ligaments repair slowly due to low blood flow and cell content. An engineered tissue contruct (ETC) approach using multi- potent bone marrow stromal cells (MSCs) without an exogenous scaffold promises a robust autologous intervention strategy. From a biomechanical perspective, two physical processes govern the development of ETCs in vitro: growth, such as protein deposition or cell proliferation, and remodeling, such as fiber reorientation or cell differentiation. This dissertation describes the development and analysis of biomechanical models of growth and remodeling critical to scaffold-less soft tissue engineering.;Firstly, the thermodynamics of a class of fiber remodeling laws were investigated in detail. It was found that purely mechanical formulations of remodeling that stiffen tissue are thermodynamically inadmissible. This dissipation imbalance was quantified in a finite-element model of tendon undergoing fiber reorientation and was found to be positive under both constant displacement and constant load boundary conditions.;Next, a novel image processing algorithm was developed to quantify directionality in planar and volumetric image data for incorporation into continuum mechanical models. With a single input parameter, the method was validated in 2D against representative synthetic images of known fiber distributions and was able to distinguish in 3D between isotropic and fibroblast-aligned collagen gels imaged using confocal microscopy.;To optimize the ETC culture system for tendon and ligament, the effects of oxygen content were studied on the growth and fibroblastic differentiation of rat MSCs and tendon fibroblasts (TFbs). A1SCs exhibited a significantly shorter population doubling time under hypoxic conditions (5% O2) compared to normoxia (18% O2). Collagen I m13,NA and protein levels increased significantly up to 2d in hypoxic MSC culture. Both cell types demonstrated elevated inR,1 As encoding the tendon and ligament-associated transcription factor scleraxis under hypoxia.;Besides the individual contributions of these studies, the ability to model and simulate complex cell and tissue behaviors---both computationally and experimentally---portends not only patient-specific engineered tissue therapies using "computer-aided tissue engineering", but also enables the testing of hypotheses related to important biological questions not directly approachable via conventional experiments.
机译：由于血流量和细胞含量低，肌腱和韧带保留在自己的装置中，修复缓慢。使用不具有外源支架的多功能骨髓基质细胞（MSC）进行的工程组织构建（ETC）方法有望实现可靠的自体干预策略。从生物力学的角度来看，体外ETC的发展有两个物理过程来控制：生长（例如蛋白质沉积或细胞增殖）和重塑（例如纤维重新定向或细胞分化）。本论文描述了对无支架软组织工程至关重要的生长和重塑的生物力学模型的发展和分析。首先，详细研究了一类纤维重塑规律的热力学。已经发现，使组织变硬的纯机械配方在热力学上是不允许的。这种耗散失衡在纤维重新定向的有限元牛筋模型中得到了定量，并且在恒定位移和恒定载荷边界条件下都为正。；接下来，开发了一种新颖的图像处理算法来量化平面和体积图像中的方向性纳入连续力学模型的数据。使用单一输入参数，该方法已针对已知纤维分布的代表性合成图像在2D中进行了验证，并能够在3D中区分出使用共聚焦显微镜成像的各向同性和成纤维细胞排列的胶原蛋白凝胶。韧带，研究了氧含量对大鼠MSCs和肌腱成纤维细胞（TFbs）的生长和成纤维细胞分化的影响。与常氧（18％O2）相比，在缺氧条件下（5％O2），A1SCs的种群倍增时间显着缩短。在缺氧的MSC培养中，胶原蛋白I m13，NA和蛋白质水平显着提高至2d。两种细胞类型均显示出在缺氧条件下编码肌腱和韧带相关转录因子硬化的inR，1 As升高。;除了这些研究的个人贡献外，还具有建模和模拟复杂细胞和组织行为的能力-在计算和实验上- -不仅可以使用“计算机辅助组织工程”来针对特定患者的组织工程疗法，而且还可以检验与重要生物学问题相关的假设，而这些假设是常规实验无法直接解决的。

著录项

  • 作者

    Olberding, Joseph E.;

  • 作者单位

    University of Michigan.;

  • 授予单位 University of Michigan.;
  • 学科 Engineering Biomedical.;Biophysics Biomechanics.;Biophysics General.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 146 p.
  • 总页数 146
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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