Rapid biomaterial-screening in zebrafish

生物材料开发是一个迭代过程，通常依赖于对材料性能的体外评估，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。最好的候选材料在小型哺乳动物模型中进行测试，以评估材料在体内的性能。众所周知，体外模型虽然经济有效且简单，但不能概括体内的环境，而且在体外表现良好的材料往往在体内失败或具有意想不到的反应。然而，将目前的小动物模型纳入材料开发的早期是不可行的，因为动物工作需要大量的资源。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，但终点数据对影响整体材料性能的过程的洞察有限。最近，斑马鱼因其体积小、光学透明、易于遗传操作以及适合于高分辨率、基于非侵入性图像的生物过程分析而成为一种强大和强大的动物模型。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、预测和经济高效地在体内表征生物材料，以改进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，在接下来的五年中，将提出三个研究目标，并将培养两名硕士、两名博士和四名本科生：目标1：通过定义生物材料微植入的关键参数和技术，开发一个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性的实验条件。目标2：利用非侵入性荧光显微镜技术设计基于斑马鱼的生物材料表征方法，以评估微粒降解和药物释放动力学。目标3：利用带有荧光标记细胞群的转基因斑马鱼菌株建立生物材料宿主反应筛选试验，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、炎症、炎症和药物释放动力学拟议的研究将对生物材料和生物医学工程领域产生重大影响，因为它将开发用于体内生物材料表征的新工具，从而能够选择具有良好预测临床性能的更好的候选材料。

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.