Manipulating the chemistry and nanotopography of cultured diatoms for the application in tissue regeneration technologies

操纵培养硅藻的化学和纳米形貌以应用于组织再生技术

• 批准号: 2279784
• 金额: --
• 依托单位: Queen's University Belfast
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2279784
• 关键词: Manipulating; chemistry; nanotopography; cultured; diatoms

The overall objectives of this PhD are to investigate the ability of diatoms (microalgae) to uptake and incorporate a selection of metal ions into their silica cell walls (known as frustules). This is intended to be achieved via a simple "in-vivo culturing" method, in which the salts of the desired metals are dissolved into the diatoms' culture medium. Once we confirm successful uptake, we will then shift the focus to optimise the conditions for maximum metal ion uptake, through altering the culturing conditions. After the diatoms have incorporated the metal ions they will then be characterised, with particular attention to any chemical or physical changes that occur post metal uptake.As stated above we will culture our own diatoms, provided by our collaborators (Dr Matthew Julius, St Cloud State University), and vary multiple conditions and parameters, such as concentrations of metals and nutrients, to available lighting etc. Once the diatoms have been successfully grown their metal uptake will be measured through a range of analytical techniques. The metal ions that are incorporated into the frustule may change the nanotopography (mainly pore distribution and size), and any ions that are incorporated into the organic phase may change the composition of fatty acids. To analyse the physical/structural features, methods such as AFM, EDX, SEM and TGA will be used. For the chemical/fatty acid analysis, methods used will include GCMS & ICP.We will use these techniques to monitor metal incorporation and try to optimise conditions to allow for maximum uptake. After this stage dissolution studies may be carried out to try and determine the metal ion release kinetics. This research is of particular interest for two key reasons:Firstly, this research should shed light on the process by which diatoms take up and incorporate metals into their frustules - prior work has shown that Ca and Ti are incorporated into frustules, however not a great amount of detail is known about the process. Therefore, we wish to extend the database of metals known to be utilised by diatoms, and further understand what effects these metal ions have on the biochemistry and frustule structure. The other core reason for this research being of interest is the potential applications in biomaterial technology that may be derived and further developed from the understanding this research will provide. Diatoms themselves produce very intricate porous nanostructures that are perfectly replicated each generation, and with precision that would be hard to replicate from current nanofabrication processes (which are extremely costly and utilise hazardous materials). If we can harness these biological nanofabricating "factories" and begin doping these frustules with substitute metal ions we may have a more environmentally friendly & inexpensive pathway to nanomaterials. We can then tune these structures with the ions being incorporated - within our research we have chosen particular metal ions that have been shown within the current literature to have beneficial effects on bone cells to inspire bone regeneration and increase bone density (therefore, may be the preliminary research to inspire new drugs/therapies for bone deterioration diseases like osteoporosis).To now there are not many hassle free implantable materials that do not cause an immune response, and other porous nanomaterials are difficult and expensive to manufacture, typically requiring hazardous chemicals, It has already been shown that "diatom biosilica is non-toxic and does not invoke a pro-inflammatory response", therefore offering a relatively benign and inexpensive pathway to highly porous implantable nanostructures, and hopefully they will be shown to incorporate metal ions that in one way or another help bone healing / regeneration.

这个博士学位的总体目标是研究硅藻（微藻）吸收并将选择的金属离子纳入其二氧化硅细胞壁（称为硅藻壳）的能力。这旨在通过简单的"体内培养"方法来实现，其中将所需金属的盐溶解到硅藻的培养基中。一旦我们确认成功摄取，我们将转移重点，通过改变培养条件来优化最大金属离子摄取的条件。在硅藻掺入金属离子后，将对它们进行表征，特别注意金属吸收后发生的任何化学或物理变化。如上所述，我们将培养我们自己的硅藻，由我们的合作者提供（马修·朱利叶斯博士，圣克劳德州立大学），并改变多个条件和参数，如金属和营养物质的浓度，一旦硅藻成功生长，将通过一系列分析技术测量其金属吸收。掺入硅藻壳中的金属离子可以改变纳米形貌（主要是孔分布和尺寸），并且掺入有机相中的任何离子都可以改变脂肪酸的组成。为了分析物理/结构特征，将使用AFM、EDX、SEM和TGA等方法。对于化学/脂肪酸分析，使用的方法将包括GCMS和ICP。我们将使用这些技术来监测金属的掺入，并尝试优化条件，以允许最大的吸收。在该阶段之后，可以进行溶解研究以尝试和确定金属离子释放动力学。这项研究是特别感兴趣的两个关键原因：首先，这项研究应该阐明硅藻采取并将金属纳入其硅藻壳的过程-先前的工作表明，钙和钛被纳入硅藻壳，但没有大量的细节是已知的过程。因此，我们希望扩展已知被硅藻利用的金属数据库，并进一步了解这些金属离子对生物化学和硅藻壳结构的影响。这项研究的另一个核心原因是生物材料技术的潜在应用，这些应用可能会从这项研究提供的理解中衍生和进一步发展。硅藻本身产生非常复杂的多孔纳米结构，每一代都能完美复制，而且精确度很难从目前的纳米纤维工艺中复制（成本极高，使用有害材料）。如果我们能够利用这些生物纳米制造"工厂"，并开始用替代金属离子掺杂这些硅藻壳，我们可能会有一个更环保和廉价的纳米材料途径。然后，我们可以调整这些结构与离子被纳入-在我们的研究中，我们已经选择了特定的金属离子，已被证明在目前的文献中对骨细胞有有益的影响，以激发骨再生和增加骨密度（因此，可能是启发骨质疏松症等骨退化疾病的新药/疗法的初步研究）到目前为止，没有多少不引起免疫反应的无麻烦的可植入材料，并且其他多孔纳米材料制造起来困难且昂贵，通常需要危险化学品。已经表明"硅藻生物二氧化硅是无毒的并且不会引起促炎反应"，因此，为高度多孔的可植入纳米结构提供了一种相对良性和廉价的途径，并且希望它们将显示出掺入以某种方式帮助骨愈合/再生的金属离子。