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A biocompatible, heparin-binding polycation for the controlled delivery of growth factors.

机译：一种生物相容性，肝素结合性聚阳离子，用于控制生长因子的递送。

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摘要

The delivery of growth factors has been attempted for a number of different therapies. The approach of delivering therapeutic growth factors in a safe and efficient manner is difficult and certain criteria should be met. These criteria include: binding the appropriate growth factors, maintaining their bioactivity, and delivering these proteins with controllable release kinetics for an extended period of time. These criteria encompass a set of guidelines that hope to mimic in vivo biological events such as neovascularization. The central goal of this thesis is to meet these criteria by introducing a novel delivery strategy for growth factors using a biocompatible polycation and heparin.;It was hypothesized that a polycation could interact with heparin to form a complex with the potential to deliver bioactive growth factors with an adaptable release. This hypothesis was tested by examining the release kinetics of bFGF from the complex and investigating whether the released bFGF maintained its bioactivity. The [polycation:heparin:bFGF] complex was formed by mixing the components in water, resulting in a precipitate. This precipitate was able to deliver bFGF with controllable release kinetics and the bioactivity of the released bFGF was higher than bolus bFGF and comparable to heparin stabilized bFGF. This system is expected to have the ability to bind and deliver numerous heparin-binding growth factors.;In conclusion, the delivery system developed in this research provides a novel mechanism for controlled release of growth factors. This delivery strategy has met the criteria listed earlier and this research has laid the foundation for a successful delivery vehicle. Further, a biocompatible polycation was synthesized, which is a critical component of the delivery system. This polycation exhibited in vitro and in vivo biocompatibility that was orders of magnitude higher than existing polycations and has the potential to be very useful in a variety of biomedical applications. This design principle is also expected to serve as a platform for the synthesis of other biocompatible polycations.
机译：已经尝试了多种不同疗法来递送生长因子。以安全有效的方式递送治疗性生长因子的方法是困难的，应满足某些标准。这些标准包括：结合适当的生长因子，维持其生物活性，并在延长的时间段内以可控的释放动力学传递这些蛋白质。这些标准涵盖了一组指南，希望能模仿体内生物事件，例如新血管形成。本论文的主要目标是通过使用生物相容性聚阳离子和肝素为生长因子引入新的递送策略来满足这些标准;假设聚阳离子可以与肝素相互作用形成复合物，具有递送生物活性生长因子的潜力具有可调整的版本。通过检查复合物中bFGF的释放动力学并研究释放的bFGF是否保持其生物活性来检​​验该假设。通过将组分在水中混合形成[聚阳离子：肝素：bFGF]复合物，从而产生沉淀。该沉淀物能够递送具有可控的释放动力学的bFGF，并且所释放的bFGF的生物活性高于大剂量bFGF，并且与肝素稳定的bFGF相当。预期该系统具有结合和递送多种肝素结合生长因子的能力。总之，本研究开发的递送系统提供了控制生长因子释放的新机制。该交付策略已满足前面列出的标准，这项研究为成功的交付工具奠定了基础。此外，合成了生物相容性聚阳离子，其是递送系统的关键组分。该聚阳离子表现出比现有聚阳离子高几个数量级的体外和体内生物相容性，并且在多种生物医学应用中具有非常有用的潜力。该设计原理也有望用作合成其他生物相容性聚阳离子的平台。

著录项

  • 作者

    Zern, Blaine J.;

  • 作者单位

    Georgia Institute of Technology.;

  • 授予单位 Georgia Institute of Technology.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 149 p.
  • 总页数 149
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;
  • 关键词

  • 入库时间 2022-08-17 11:38:28

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