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Scaffold design parameters to stimulate the osteogenic signal expression for bone tissue engineering applications.

机译：支架设计参数可刺激骨组织工程应用中的成骨信号表达。

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摘要

The fundamental components of bone tissue engineering are (a) progenitor cells which subsequently express tissue matrix, (b) scaffolds which can act as temporary frameworks to support bone growth, and (c) growth factors to induce osteoblast regeneration. A variety of growth factors are involved during the differentiation cascade and these chemical and biological signals dynamically interact with cell populations to facilitate the differentiation. Therefore, enhanced expression of endogenous growth factor genes might facilitate abundant existence of growth factors in the surrounding microenvironment, stimulate the osteogenic differentiation of progenitor cell population, and finally induce bone regeneration. This work is focused on the augmentation of osteogenic signal expressions to stimulate the downstream differentiation of transplanted bone marrow stromal cells (BMSCs) population through the optimization of a variety of properties of three dimensional (3D) biodegradable poly(propylene fumarate) (PPF) scaffold. Changes in the microenvironment of cell population would affect the responses of localized cell population and the manipulated scaffold properties might be associated with induction of endogenous osteogenic signal expressions.;First, the effect of cell-to-cell paracrine signaling distance, which can by modulated by initial cell seeding density, on the osteogenic signal expressions and osteoblastic differentiation of BMSCs on 2D PPF disks was investigated. Next, in order to investigate the improvement of the 3D macroporous PPF scaffold by the incorporation with nanoparticle filler materials, PPF/hydroxyapatite (HA) nanocomposite scaffolds were fabricated. The effect of HA content and initial cell seeding density on the osteogenic signal expression in 3D porous system was then determined. Finally, the incorporation of diethyl dumarate (DEF) with PPF was tested based on the photocrosslinking characteristics of PPF/DEF composite material with increased mechanical properties. The effect of two scaffold design parameters including the stiffness by modulating the DEF content as well as the pore size of porous scaffold on the signal expression and downstream osteoblastic differentiation was investigated. In addition, the feasibility of PPPF/DEF materials for stereolithographical fabrication was also tested in this work.;Controlling these construction parameters to optimize engineered bone substitutes could affect various cellular functions of attachment, proliferation, signal expression, and differentiation. This research provided the insight of stimulation of the expression of target endogenous genes to induce the osteogenic differentiation and bone regeneration as well as the fabrication of improved bone substitute implant materials which is clinically applicable.
机译：骨组织工程的基本组成部分是（a）随后表达组织基质的祖细胞，（b）可以充当支持骨骼生长的临时框架的支架，以及（c）诱导成骨细胞再生的生长因子。在分化级联过程中涉及多种生长因子，并且这些化学和生物信号与细胞群体动态相互作用以促进分化。因此，增强内源性生长因子基因的表达可能促进周围微环境中生长因子的大量存在，刺激祖细胞群体的成骨分化，并最终诱导骨再生。这项工作的重点是通过优化三维（3D）可生物降解的聚富马​​酸丙二酯（PPF）支架的各种特性来增强成骨信号表达，以刺激移植的骨髓基质细胞（BMSCs）群体的下游分化。 。细胞群体微环境的变化会影响局部细胞群体的反应，操纵的支架特性可能与内源性成骨信号表达的诱导有关。首先，细胞间旁分泌信号距离的影响可以通过调节通过初始细胞接种密度，研究了二维PPF盘上BMSCs的成骨信号表达和成骨细胞分化。接下来，为了研究通过掺入纳米颗粒填充材料对3D大孔PPF支架的改进，制备了PPF /羟基磷灰石（HA）纳米复合支架。然后确定HA含量和初始细胞接种密度对3D多孔系统中成骨信号表达的影响。最终，基于PPF / DEF复合材料具有增强的机械性能的光交联特性，测试了PPF与杜马酸二乙酯（DEF）的结合。研究了两个支架设计参数，包括通过调节DEF含量的刚度以及多孔支架的孔径对信号表达和下游成骨细胞分化的影响。此外，这项工作还测试了PPPF / DEF材料在立体光刻加工中的可行性。控制这些构造参数以优化工程骨替代物可能会影响细胞的各种附着，增殖，信号表达和分化功能。该研究提供了刺激靶内源性基因表达以诱导成骨分化和骨再生的见识，以及提供了可在临床上应用的改良的骨替代植入物材料。

著录项

  • 作者

    Kim, Kyobum.;

  • 作者单位

    University of Maryland, College Park.;

  • 授予单位 University of Maryland, College Park.;
  • 学科 Engineering Biomedical.;Engineering Chemical.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 214 p.
  • 总页数 214
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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