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Stimulation of bone marrow stromal cells in the development of tissue engineered ligaments.

机译：在组织工程韧带的发展中刺激骨髓基质细胞。

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摘要

The anterior cruciate ligament's (ACL) inability to heal post-rupture makes it an attractive target for tissue engineering studies, which support a large clinical need. Development of a fully functional ACL in vitro would provide an efficacious alternative to inadequate current repair options, as well as serving as a tissue model for biomedical research. The objective of this work was to develop a process by which ligament tissue can be generated in vitro, utilizing the sequential application of biochemical and mechanical stimulation. The goal was to monitor the developmental state of adult stem cell seeded constructs, correlating cell response to applied stimulation to further matrix in-growth and tissue development. Initially, bone marrow stromal cell (BMSC) behavior was studied in response to growth factor and medium supplementation, and the combination of biochemical stimulation was identified that supported induction toward fibroblast lineage. In selection of an appropriate biomaterial for three dimensional culture, surface modified silk fibers imparted greater mechanical integrity to tissue engineered constructs and equivalent biocompatibility as compared to cross-linked collagen fibers. BMSC seeded silk matrices responded to the sequential administration of growth factors in static culture with enhanced differentiation and ligament specific extracellular matrix (ECM) production. Sequential stimulation was further explored with the transition of growth factors to dynamic culture to enhance cell specific differentiation and matrix remodeling characteristic of the native ACL. Dynamic culture enhanced BMSC differentiation and the production of ligament specific ECM, providing the framework for in vitro stimulation of ligament development. In summary, an appropriate cell source, biomaterial, and stimulatory regime were combined for in vitro ligament development. The approach and methodology identified in this study offers direction for tissue engineering strategies addressing current clinical needs.
机译：前交叉韧带（ACL）无法治愈骨折后，使其成为组织工程研究的有吸引力的靶标，可满足大量的临床需求。体外功能齐全的ACL的开发将提供一种有效的替代方法，以替代当前不足的修复方案，并作为生物医学研究的组织模型。这项工作的目的是利用生物化学和机械刺激的顺序应用，开发一种可以在体外产生韧带组织的方法。目的是监测成年干细胞接种构建物的发育状态，将细胞对施加刺激的反应与基质进一步向内生长和组织发育相关联。最初，研究了骨髓基质细胞（BMSC）响应生长因子和培养基补充的行为，并确定了生化刺激的组合可支持对成纤维细胞谱系的诱导。在选择合适的生物材料进行三维培养时，与交联的胶原纤维相比，表面改性的丝纤维赋予组织工程构造更大的机械完整性，并具有同等的生物相容性。 BMSC种子丝基质对静态培养中生长因子的顺序给药有增强的分化和韧带特异性细胞外基质（ECM）产生的反应。随着生长因子向动态培养的过渡，进一步探索了顺序刺激，以增强天然ACL的细胞特异性分化和基质重塑特性。动态培养增强了BMSC的分化和韧带特异性ECM的产生，为体外刺激韧带发育提供了框架。总之，将适当的细胞来源，生物材料和刺激机制结合起来，用于体外韧带发育。本研究中确定的方法和方法为解决当前临床需求的组织工程策略提供了指导。

著录项

  • 作者

    Moreau, Jodie E.;

  • 作者单位

    Tufts University.;

  • 授予单位 Tufts University.;
  • 学科 Engineering Biomedical.; Biology Cell.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 192 p.
  • 总页数 192
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;细胞生物学;
  • 关键词

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