A dynamic biomaterial-ligand tethering strategy for tissue engineering

组织工程的动态生物材料-配体束缚策略

• 批准号: 2267412
• 金额: --
• 依托单位: University of York
• 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-2267412
• 关键词: dynamic; biomaterial; ligand; tethering; strategy

The use of biomaterials to drive the repair, regrowth, or regeneration of damaged biologicaltissue has the potential to revolutionise the treatment of disease. Materials that can presentcells and tissues with powerful biochemical signals, through attached peptides, proteins, andcarbohydrates, are particularly effective at controlling regeneration. However, at present westruggle to grow mature, fully-functioning tissues that can be used in the clinic due to thedifficulty of controlling these signalling events. While nature relies on intricate networks oftightly controlled, dynamic signalling to drive repair, this is in stark contrast to the staticsignals provided by synthetic materials. In this PhD project, we therefore aim to develop newchemistries that allow the reversible attachment of peptide and proteins to biomaterialscaffolds.We will particularly focus on the development of novel conjugation chemistries that allowproteins to be covalently attached to material surfaces via stabilised imines. We will identifyconditions that allow subsequent cleavage of the protein under biocompatible conditions,while regenerating the original reactive groups on the material surface. By doing so, we willenable the attachment of a second signalling protein that can itself be cleaved, allowingiterative cycles of protein presentation. This would represent a major advance in biomaterialschemistry, allowing us to take a major step towards mimicking the complexity of naturaltissues. Key to this goal is the optimisation of the underlying conjugation chemistry, requiringprecise understanding of the reaction equilibria and kinetics which we will study using acombination of photo-physical and materials chemistry techniques. We will then go on toapply our novel chemistries in the design of new biomaterials for cartilage regeneration, bysequentially presenting growth factor signalling proteins that drive tissue development fromcell growth through to tissue maturation.

使用生物材料来驱动受损生物组织的修复、再生或再生有可能彻底改变疾病的治疗方法。通过附着的肽、蛋白质和碳水化合物，可以向细胞和组织提供强大的生化信号的材料在控制再生方面特别有效。然而，由于控制这些信号事件的困难，目前我们很难培育出可用于临床的成熟、功能齐全的组织。虽然大自然依赖于严格控制的复杂网络，动态信号来驱动修复，但这与合成材料提供的静态信号形成鲜明对比。因此，在这个博士项目中，我们的目标是开发新的化学物质，使肽和蛋白质可逆地附着到生物材料支架上。我们将特别关注开发新型共轭化学物质，使蛋白质通过稳定的亚胺共价附着到材料表面。我们将确定允许在生物相容性条件下随后裂解蛋白质的条件，同时在材料表面上再生原始反应基团。通过这样做，我们将能够附着第二种信号蛋白，该信号蛋白本身可以被切割，从而允许蛋白质呈递的迭代循环。这将代表生物材料化学的重大进步，使我们能够在模仿自然组织的复杂性方面迈出重要一步。这一目标的关键是优化基础共轭化学，需要精确理解反应平衡和动力学，我们将结合光物理和材料化学技术进行研究。然后，我们将继续将我们的新化学物质应用于软骨再生的新生物材料的设计中，依次呈现驱动组织发育（从细胞生长到组织成熟）的生长因子信号蛋白。