Rapid biomaterial-screening in zebrafish

斑马鱼生物材料的快速筛选

• 批准号: RGPIN-2015-06166
• 负责人: Fitzpatrick, Lindsay
• 金额: $ 2.19万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=708338
• 关键词: Rapid; biomaterial; screening; zebrafish

Biomaterial development is an iterative process that typically relies upon in vitro assessment of material propertie, such as degradation, drug release, bioconjugate activity and biocompatibility, to select and optimize candidate materials. The top candidates are tested in small mammalian models to assess the material performancein vivo. It is well recognized that in vitro models, although cost effective and simple, cannot recapitulate the in vivo environment and often materials that performed well in vitro fail or have unanticipated responses in vivo. However, it is not feasible to incorporate the current small animal models early in material development due to the significant resources that are required for animal work. Furthermore, while mammalian models provide important insights into outcomes of host responses and biomaterial performance, the endpoint data provide limited insight into the processes that contribute to the overall material performance. Recently, zebrafish have emerged as a powerful and robust animal model due to their small size, optical transparency, ease of genetic manipulation and their amenability to high-resolution, non-invasive image-based analysis of biological processes. Despite these numerous advantages, zebrafish have had very limited use in the field of biomaterials. The long-term vision of my proposed research program is to establish a zebrafish biomaterial-screening platform capable of rapid, predictive and cost effective in vivo characterization of biomaterials to improve the selection and optimization of candidate materials for biomedical applications. To achieve this long-term goal, three research objectives will be addressed over the next five years, and will train 2 MASc, 2 PhD and 4 undergraduate students: Objective 1: The development of a zebrafish biomaterial-screening platform by defining critical parameters and techniques for biomaterial micro-implantation that yield reproducible experimental conditions for evaluating biomaterial characteristics in zebrafish. Objective 2: Design zebrafish-based biomaterial characterization assays using non-invasive fluorescent microscopy techniques to evaluate microparticle degradation and drug release kinetics. Objective 3: Develop a biomaterial host response screening assay using transgenic zebrafish strains with fluorescently labelled cell populations to model general biomaterial host responses that may adversely affect biomaterial performance, including inflammation, calcification and fibrous encapsulation. The proposed research will have significant impact the fields of biomaterials and biomedical engineering by developing novel tools for in vivo biomaterial characterization that will enable the selection of better material candidates with well-predicted clinical performance.

生物材料开发是一个迭代过程，通常依赖于对材料性能（如降解、药物释放、生物结合活性和生物相容性）的体外评估，以选择和优化候选材料。在小型哺乳动物模型中测试了最佳候选物，以评估材料的体内性能。众所周知，体外模型虽然具有成本效益且简单，但不能概括体内环境，并且通常在体外表现良好的材料在体内失效或具有非预期的反应。然而，由于动物工作需要大量资源，因此在材料开发早期纳入当前的小动物模型是不可行的。 此外，虽然哺乳动物模型为宿主反应和生物材料性能的结果提供了重要的见解，但终点数据对有助于整体材料性能的过程提供了有限的见解。 最近，斑马鱼已经成为一个强大的和强大的动物模型，由于其体积小，光学透明，易于遗传操作和他们的顺从性，高分辨率，非侵入性的基于图像的生物过程的分析。尽管有这些众多的优点，但斑马鱼在生物材料领域的应用非常有限。我提出的研究计划的长期愿景是建立一个斑马鱼生物材料筛选平台，能够快速，预测和成本效益的生物材料的体内表征，以改善生物医学应用的候选材料的选择和优化。为了实现这一长期目标，三个研究目标将在未来五年内解决，并将培养2个硕士，2个博士和4个本科生： 目标一：通过定义生物材料微植入的关键参数和技术，开发斑马鱼生物材料筛选平台，以获得可重现的实验条件，用于评估斑马鱼的生物材料特性。 目标二：设计基于斑马鱼的生物材料表征分析，使用非侵入性荧光显微镜技术来评估微粒降解和药物释放动力学。 目标三：开发一种生物材料宿主反应筛选试验，该试验使用具有荧光标记细胞群的转基因斑马鱼品系，以模拟可能对生物材料性能产生不利影响的一般生物材料宿主反应，包括炎症、钙化和纤维包裹。 拟议的研究将通过开发用于体内生物材料表征的新工具，对生物材料和生物医学工程领域产生重大影响，这些工具将能够选择具有良好预测临床性能的更好材料候选物。