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Hyaluronan and gelatin biomaterials for bioprinting engineered tissues.

机译:透明质酸和明胶生物材料,用于生物打印工程组织。

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摘要

To address the current need for engineered tissues and organs, we have developed new hyaluronic acid (HA) and gelatin-based biomaterials for implementation within bioprinting and rotational bioreactor frameworks. By using creative modification, combination, and engineering strategies, we have been able to add novel properties and functionality to these derivatives.Based on the original thiol-functionalized HA hydrogels developed in our laboratory, we have branched out to further modify hydrogels using new chemistries and crosslinkers. Different crosslinkers, such as a 4-armed PEG crosslinker and gold nanoparticles (AuNPs), as well as a methacrylated HA derivatives, alter the gelation characteristics and mechanical properties of the hydrogels, which have been characterized by rheology. These hydrogels have properties that make them more suitable for bioprinting applications, in which the mechanical properties determine ease of material deposition into 3-D physiologically-relevant organizations. Additionally, these materials show good biocompatibility, making them appropriate for cell-loaded printing and tissue culture.We have also modified the surfaces of crosslinked dextran beads with HA and gelatin derivatives, turning them into effective microcarriers that support cell growth in a rotational bioreactor. Cell clusters that were formed using this approach could be removed from the beads and returned to culture to yield bead-free microtissues that could be bioprinted within a hydrogel carrier.The goal of this work is to demonstrate the efficacy of these materials and approaches in bioprinting applications. Tailoring the mechanical properties to the exact specifications necessary for successful printing is difficult, but possible with a logical approach, addressing each of the parameters that affect the end product -- concentrations, polymer to crosslinker ratio, gelation times, and cell densities. Use of hyaluronic acid in medicine has long been established, but by incorporating new modifications and engineering techniques, we can develop biomaterials that address issues ranging from simple cell culture procedures to advanced protocols for developing engineered tissues.
机译:为了满足当前对工程组织和器官的需求,我们开发了新的透明质酸(HA)和明胶基生物材料,可在生物印刷和旋转生物反应器框架内实施。通过使用创新的修饰,组合和工程策略,我们能够为这些衍生物添加新颖的特性和功能。基于我们实验室开发的原始硫醇官能化的HA水凝胶,我们已经扩展了使用新化学方法进一步修饰水凝胶的能力。和交联剂。不同的交联剂,例如4臂PEG交联剂和金纳米颗粒(AuNPs),以及甲基丙烯酸酯化的HA衍生物,改变了水凝胶的凝胶化特性和机械性能,这些已通过流变学表征。这些水凝胶的特性使其更适合生物打印应用,其中机械特性决定了材料沉积到3D生理相关组织中的难易程度。此外,这些材料显示出良好的生物相容性,使其适合于细胞负载的印刷和组织培养。我们还用HA和明胶衍生物修饰了交联的葡聚糖珠子的表面,将它们转变为有效的微载体,支持旋转生物反应器中的细胞生长。使用这种方法形成的细胞团可以从珠子上移出并返回培养,产生无珠子的微组织,可以在水凝胶载体中进行生物印记。这项工作的目的是证明这些材料和方法在生物印记中的功效。应用程序。将机械性能调整到成功印刷所需的确切规格是困难的,但是通过逻辑方法可以解决影响最终产品的每个参数-浓度,聚合物与交联剂的比率,胶凝时间和细胞密度。透明质酸在医学上的用途已久,但通过结合新的改良方法和工程技术,我们可以开发生物材料,以解决从简单的细胞培养程序到开发工程组织的先进方案等问题。

著录项

  • 作者

    Skardal, Aleksander.;

  • 作者单位

    The University of Utah.;

  • 授予单位 The University of Utah.;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 207 p.
  • 总页数 207
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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