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Characterisation of ceramic bone graft environments for optimised angiogenesis

表征陶瓷骨移植环境以优化血管生成

基本信息

批准号：
2118155
负责人：
金额：
--
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2118155
关键词：
Characterisation ceramic bone graft environments

项目摘要

There has been significant interest over a number of years in the use of calcium phosphate implants for skeletal repair due to their similarity in composition to the mineral component of the hard tissues in the body. However, the efficacy of bone graft substitutes is strongly influenced by their ability to support tissue in-growth and encourage angiogenesis. Previous work done by Gariboldi et al. on the 3D printing of controlled hydroxyapatite architectures as model substrates to study angiogenesis has resulted in the successful establishment techniques not only relating to the 3D printing of such substrates but also to culture the appropriate combination of cells to produce aligned micro-vessels. This result gives rise to a significant number of new ideas and possibilities to further the research area.The control of surface roughness and pore structure has recently become a very hot topic in the field of biomaterials and bioceramics field in terms of the effects on protein adsorption (e.g. from plasma). Preliminary studies will assess the nature of protein adsorption and their release kinetics. The work will move on to consider how this influences osteoclastic remodelling and osteoblast-mediated bone deposition. While mono-culture has often been used in the past, the importance of co-culture of the physiologically relevant cells is increasingly recognised as a way to provide improved understanding of the underlying mechanisms and processes of bone repair. The use of highly controlled, model 2.5D environments offers the potential to study in more detail the effects of scaffold architecture and surface roughness for the development of angiogenic and osteo-inductive bone graft substitutes.Furthermore, I intend to translate the findings made in 2.5D to the more challenging aspects of production of controlled 3D environments as part of this project. Over the course of the project, I seek to develop my expertise in live cell imaging to understand cell-cell interactions. Additionally, I will develop the skills and knowledge readily available in the research group, and explore how X-Ray microtomography (microCT) might be combined with the use of appropriate contrast agents. These include antibody conjugates for evaluation of angiogenesis and more broadly, to provide information about the role of the protein adsorption in bone repair.The outcome of the investigations will be an improved understanding of the influence of protein adsorption on bone graft substitutes on bone repair and further insights into the role of scaffold architecture and surface topography in directing cell behaviour.

由于磷酸钙植入物与体内硬组织的矿物质组分在组成上相似，因此多年来人们对磷酸钙植入物用于骨骼修复产生了极大的兴趣。然而，骨移植替代物的疗效受到其支持组织向内生长和促进血管生成的能力的强烈影响。Gariboldi等人先前在3D打印受控羟基磷灰石结构作为模型基质以研究血管生成方面所做的工作已经成功地建立了不仅与此类基质的3D打印有关的技术，而且还培养了适当的细胞组合以产生对齐的微血管。这一结果产生了大量的新的想法和可能性，进一步的研究area.The表面粗糙度和孔结构的控制，最近成为一个非常热门的话题，在生物材料和生物陶瓷领域的蛋白质吸附（如从血浆）的影响。初步研究将评估蛋白质吸附的性质及其释放动力学。这项工作将继续考虑这是如何影响骨细胞重塑和成骨细胞介导的骨沉积。虽然过去经常使用单培养，但生理相关细胞的共培养的重要性越来越被认为是一种提高对骨修复的潜在机制和过程的理解的方法。高度受控的2.5D模型环境的使用为更详细地研究支架结构和表面粗糙度对血管生成和骨诱导骨移植替代物的发展的影响提供了可能性，此外，我打算将2.5D中的发现转化为更具挑战性的可控3D环境生产方面，作为本项目的一部分。在这个项目的过程中，我寻求发展我在活细胞成像方面的专业知识，以了解细胞间的相互作用。此外，我将发展研究小组中现有的技能和知识，并探索如何将X射线显微断层扫描（microCT）与使用适当的造影剂相结合。这些包括抗体偶联物的血管生成的评价，更广泛地说，提供有关的蛋白质吸附在骨修复中的作用的信息，调查的结果将是一个更好的理解蛋白质吸附对骨移植替代品对骨修复的影响，并进一步深入了解支架结构和表面形貌在指导细胞行为的作用。