Biointerfaces: a surface science perspective

生物界面：表面科学的视角

• 批准号: RGPIN-2018-05608
• 负责人: Cerruti, Marta
• 金额: $ 5.68万
• 依托单位: McGill 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=761080
• 关键词: Biointerfaces; surface; science; perspective

The exceptional properties of bone and other strong and tough natural materials derive from their structure built from both hard minerals and soft organics. The organic component acts as a scaffold onto which minerals form and grow. This process, also known as biomineralization, is orchestrated by many proteins; due to its complexity, we still do not fully understand its molecular mechanism. Our program aims at filling some crucial gaps. For example, we want to understand how the chemical nature (charge, hydrophilicity) of the proteins influence mineral formation; or how the organic scaffold onto which the minerals deposit determines how they transform over time. Understanding this will allow us to develop strategies to either promote or inhibit mineral formation, to favor bone healing or stop calcifications that occur in unwanted locations, like the cardiovascular system. To achieve these goals, we start from studying minerals derived from bones, teeth, and pathological deposits in mice or humans. We look at their physico-chemical structure with many different techniques, focusing on the interface between the mineral and the organic scaffold. This allows us to study the very early stages of mineral formation, so that we can either inhibit or promote this process depending on our final application. To understand all the variables involved and test our strategies, we prepare synthetic models that try to reproduce the biological environment in which minerals form. For example, we have a model based on elastin, the scaffold onto which minerals are often deposited in the arteries. This model can recapitulate the mineral transformations we observed in mice, but we need to improve it to reproduce other important aspects such as the shape of the deposits. We apply the understanding we gain from studying the natural minerals and mimicking their formation in the lab to three main goals: propose strategies to stop mineral formation in arteries; coat the surface of bone implants so that they strongly bind to bone and do not fail upon extended use; and design and synthesize advanced composite materials that will be extraordinarily tough thanks to their interfaces mimicking the surface onto which biominerals naturally form and adhere to. This program will improve life quality for the millions of people needing bone surgeries or affected by cardiovascular calcification, and strengthen Canada's position as one of the leaders in advanced materials manufacturing.

骨骼和其他坚韧的天然材料的特殊特性来自于它们由硬矿物和软有机物构建的结构。有机成分充当了矿物质形成和生长的脚手架。这个过程也被称为生物矿化，是由许多蛋白质编排的；由于其复杂性，我们仍然不完全了解其分子机制。我们的计划旨在填补一些关键的空白。例如，我们想要了解蛋白质的化学性质(电荷、亲水性)如何影响矿物形成；或者矿物沉积在其上的有机支架如何决定它们如何随着时间的推移而变化。了解这一点将使我们能够开发出促进或抑制矿物质形成的策略，促进骨骼愈合或阻止发生在不想要的位置的钙化，比如心血管系统。为了实现这些目标，我们从研究从老鼠或人类的骨骼、牙齿和病理沉积物中提取的矿物质开始。我们用许多不同的技术观察它们的物理化学结构，重点放在矿物和有机支架之间的界面上。这使我们能够研究矿物形成的非常早期的阶段，因此我们可以根据我们的最终应用来抑制或促进这一过程。为了理解所有涉及的变量并测试我们的策略，我们准备了合成模型，试图重现矿物形成的生物环境。例如，我们有一个基于弹性蛋白的模型，弹性蛋白是一种支架，矿物质经常沉积在动脉中。这个模型可以概括我们在老鼠身上观察到的矿物质变化，但我们需要对其进行改进，以重现其他重要方面，如沉积物的形状。我们将从研究天然矿物和在实验室中模拟其形成过程中获得的理解应用于三个主要目标：提出阻止动脉中矿物形成的策略；在骨植入物的表面涂覆一层，使其与骨骼牢固结合，并且在长期使用时不会失败；设计和合成先进的复合材料，由于其界面模仿生物矿物自然形成和附着的表面，因此将非常坚韧。该计划将改善数百万需要进行骨手术或受心血管钙化影响的人的生活质量，并加强加拿大作为先进材料制造领先者之一的地位。