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: $ 4.37万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=747134
• 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.

生物材料的开发是一个迭代的过程，通常依赖于材料特性的体外评估，如降解、药物释放、生物偶联活性和生物相容性，以选择和优化候选材料。在小型哺乳动物模型中对最佳候选材料进行测试，以评估材料在体内的性能。众所周知，体外模型虽然成本有效且简单，但不能概括体内环境，并且在体外表现良好的材料通常会失败或在体内产生意想不到的反应。然而，由于动物工作需要大量的资源，在材料开发的早期纳入目前的小动物模型是不可行的。此外，虽然哺乳动物模型对宿主反应和生物材料性能的结果提供了重要的见解，但终点数据对促进材料整体性能的过程提供了有限的见解。最近，斑马鱼由于其体积小、光学透明、易于遗传操作以及适合高分辨率、非侵入性的基于图像的生物过程分析而成为一种强大而健壮的动物模型。尽管有这些优点，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，预测和成本有效地在体内表征生物材料，以改善生物医学应用候选材料的选择和优化。为了实现这一长期目标，将在未来五年内实现三个研究目标，并将培养2名硕士生，2名博士和4名本科生：目标1：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，为评估斑马鱼的生物材料特性提供可重复的实验条件。目的2：设计基于斑马鱼的生物材料表征试验，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。目的3：利用荧光标记细胞群的转基因斑马鱼菌株开发生物材料宿主反应筛选试验，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、钙化和纤维包封。该研究将对生物材料和生物医学工程领域产生重大影响，通过开发新的体内生物材料表征工具，可以选择具有良好预测临床性能的更好的候选材料。