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首页> 外文学位 >Enhanced in vivo angiogenesis within a model tissue engineered construct using biodegradable microspheres containing encapsulated VEGF.
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Enhanced in vivo angiogenesis within a model tissue engineered construct using biodegradable microspheres containing encapsulated VEGF.

机译：使用包含胶囊化VEGF的可生物降解微球，可在模型组织工程构建体中增强体内血管生成。

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摘要

Introduction. Tissue engineering techniques offer a potential means to develop a tissue engineered construct (TEC) for the treatment of tissue and organ deficiencies. However, a lack of adequate vascularization is a limiting factor in the development of most viable engineered tissues. Vascular endothelial growth factor (VEGF) could aid in the development of a viable vascular network within TECs. The long-term goals of this research are to develop clinically relevant, appropriately vascularized TECs for use in humans. This project tested the hypothesis that the delivery of VEGF via controlled release from biodegradable microspheres would increase the vascular density and rate of angiogenesis within a model TEC.; Materials and methods. Biodegradable VEGF-encapsulated microspheres were manufactured using a novel method entitled the Solid Encapsulation/Single Emulsion/Solvent Extraction technique. Using a PLGA/PEG polymer blend, microspheres were manufactured and characterized in vitro. A model TEC using fibrin was designed for in vivo tissue engineering experimentation. At the appropriate timepoint, the TECs were explanted, and stained and quantified for CD31 using a novel semi-automated thresholding technique.; Results. In vitro results show the microspheres could be manufactured, stored, degrade, and release biologically active VEGF. The in vivo investigations revealed that skeletal muscle was the optimal implantation site as compared to dermis. In addition, the TECs containing fibrin with VEGF demonstrated significantly more angiogenesis than the controls. The TECs containing VEGF microspheres displayed a significant increase in vascular density by day 10. Furthermore, TECs containing VEGF microspheres had a significantly increased relative rate of angiogenesis from implantation day 5 to day 10.; Conclusions. A novel technique for producing microspheres loaded with biologically active proteins was developed. A defined concentration of microspheres can deliver a quantifiable level of VEGF with known release kinetics. A novel model TEC for in vivo tissue engineering investigations was developed. VEGF and VEGF microspheres stimulate angiogenesis within the model TEC. This investigation determined that biodegradable rhVEGF 165-encapsulated microspheres increased the vascular density and relative rate of angiogenesis within a model TEC. Future applications could include the incorporation of microvascular fragments into the model TEC and the incorporation of specific tissues, such as fat or bone.
机译：简介。组织工程技术提供了开发用于处理组织和器官缺陷的组织工程构建体（TEC）的潜在手段。但是，缺乏足够的血管形成是大多数可行的工程组织发展的限制因素。血管内皮生长因子（VEGF）可以帮助在TECs中建立可行的血管网络。这项研究的长期目标是开发临床相关的，适当血管化的TEC，以供人类使用。该项目检验了以下假设：通过从可生物降解微球中控释释放的VEGF可以增加模型TEC中的血管密度和血管生成速率。 材料和方法。使用称为固体包封/单乳液/溶剂萃取技术的新型方法制造了可生物降解的VEGF包封的微球。使用PLGA / PEG聚合物共混物，制备了微球，并在体外进行了“斜体”表征。设计了使用纤维蛋白的TEC模型，用于体内组织工程实验。在适当的时间点，使用新型的半自动阈值技术将TECs移出，并对CD31进行染色和定量。 结果。体外结果表明，微球可以制备，储存，降解和释放具有生物活性的VEGF。 in vivo 研究表明，与真皮相比，骨骼肌是最佳的植入部位。此外，含有纤维蛋白和VEGF的TECs的血管生成能力明显高于对照组。从植入第5天到第10天，含有VEGF微球的TECs显示血管密度显着增加。 结论。开发了一种生产载有生物活性蛋白的微球的新技术。限定浓度的微球可以以已知的释放动力学递送可定量水平的VEGF。开发了一种新型的用于体内组织工程研究的模型TEC。 VEGF和VEGF微球刺激TEC模型内的血管生成。这项研究确定了可生物降解的rhVEGF 165 包裹的微球提高了模型TEC内的血管密度和血管新生的相对速率。未来的应用可能包括将微血管碎片整合到TEC模型中，以及整合特定组织（例如脂肪或骨骼）。

著录项

  • 作者

    King, Timothy Wells.;

  • 作者单位

    The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences.;

  • 授予单位 The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences.;
  • 学科 Engineering Biomedical.; Biophysics Medical.; Health Sciences Medicine and Surgery.
  • 学位 Ph.D.
  • 年度 2000
  • 页码 147 p.
  • 总页数 147
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;生物物理学;
  • 关键词

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