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Elucidating the biological performance of decellularized bovine pericardium: Understanding macrophage polarization and functional response .

机译:阐明脱细胞牛心包的生物学性能:了解巨噬细胞极化和功能反应。

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摘要

At present, no clinically available heart valve replacement completely replicates the performance, function and remodeling capability of a native valve. As the demand for valve replacements increases, there is a need for innovative valve scaffolds such as decellularized tissue matrices. Unfortunately, the mechanisms responsible for the poor clinical performance of bioprosthetic valves is not understood, and similar mechanisms may plague future scaffolds. Explant studies consistently demonstrate the presence of macrophages on failed valve surfaces, but it is unclear whether the presence of macrophages on these materials is a cause, consequence or coincidence. This thesis explores the functional and morphological interactions of macrophages with decellularized tissue matrices in vitro in an effort to understand and predict the biological performance of these materials.;This thesis provides insights into the functional differences in three human macrophage model systems and thereby increases our understanding of macrophage interactions with collagenous biomaterials. Such knowledge is valuable for the development of better tissue heart valve replacements and for the design of collagen-based tissue-engineering scaffolds in general.;The macrophage response to decellularized bovine pericardium (DBP), a representative tissue-engineering substrate, was compared to two control polymers: medical grade polydimethylsiloxane (PDMS) and tissue culture polystyrene (TCPS). Phorbol myristate acetate-differentiated U937 cells on DBP contained less esterase and acid phosphatase activity compared to controls and were less multinucleated. Human monocyte-derived macrophages (MDMs) (trypsinized after 14 d differentiation on TCPS) that were cultured on DBP responded very similarly, validating the use of U937 cells for predicting MDM interactions with collagen. When human MDMs were differentiated directly onto the materials of interest, further observations were made. In general, MDMs on the DBP surface released low amounts of cytokines and MMP-1, with the exception of IL-6, IL-8 and MCP-1. Additionally, directly differentiated differed from trypsinized MDMs by displaying lower overall extracellular and intracellular esterase and acid phosphatase activity on all three surfaces. Although the characterization of the MDM polarization on each surface was not conclusive, this thesis provides some of the first in vitro evidence that macrophages on decellularized tissue matrices may be stimulated towards a more wound healing phenotype.
机译:目前,没有临床上可用的心脏瓣膜置换术能够完全复制天然瓣膜的性能,功能和重塑能力。随着对瓣膜替换的需求增加,需要创新的瓣膜支架,例如脱细胞的组织基质。不幸的是,导致生物人工瓣膜不良临床表现的机制尚不清楚,并且类似的机制可能困扰未来的支架。外植体研究一致地证明失败的瓣膜表面上存在巨噬细胞,但尚不清楚这些材料上是否存在巨噬细胞是原因,结果还是巧合。本论文探讨了巨噬细胞与脱细胞组织基质在体外的功能和形态相互作用,旨在了解和预测这些材料的生物学性能。;本论文提供了对三种人类巨噬细胞模型系统功能差异的见解,从而加深了我们的理解巨噬细胞与胶原生物材料的相互作用这些知识对于开发更好的组织心脏瓣膜替代物和总体上基于胶原的组织工程支架而言是有价值的。;将巨噬细胞对脱细胞牛心包膜(DBP)(一种代表性的组织工程底物)的巨噬细胞反应与两种对照聚合物:医用级聚二甲基硅氧烷(PDMS)和组织培养聚苯乙烯(TCPS)。与对照相比,DBP上的肉豆蔻酸乙酸豆蔻酸酯分化的U937细胞所含的酯酶和酸性磷酸酶活性较对照少,并且多核化程度也较低。在DBP上培养的人单核细胞衍生巨噬细胞(MDM)(在TCPS分化14天后用胰蛋白酶消化)的反应非常相似,验证了U937细胞可用于预测MDM与胶原蛋白的相互作用。当将人类MDM直接区分到感兴趣的材料上时,将进行进一步观察。通常,除IL-6,IL-8和MCP-1外,DBP表面的MDM释放少量的细胞因子和MMP-1。此外,直接分化与胰蛋白酶消化的MDM的不同之处在于,在所有三个表面上都显示出较低的总体细胞外和细胞内酯酶和酸性磷酸酶活性。虽然在每个表面上的MDM极化的表征不是结论性的,但本论文提供了一些最初的体外证据,即脱细胞组织基质上的巨噬细胞可能被刺激为更伤口愈合的表型。

著录项

  • 作者单位

    Dalhousie University (Canada).;

  • 授予单位 Dalhousie University (Canada).;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 175 p.
  • 总页数 175
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 非洲史;
  • 关键词

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