Biomaterials by design

生物材料设计

• 批准号: RGPIN-2020-06013
• 负责人: Sefton, Michael
• 金额: $ 5.54万
• 依托单位: University of Toronto
• 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=747267
• 关键词: Biomaterials; design

Materials used in healthcare and the devices based on these materials generate a biological response and control of that response dictates the successful use of the device. We will build on a suite of materials based on methacrylic acid (MAA) that has unique regenerative properties, notably, but not only, the capacity to regenerate blood vessels without any biological components. Such regenerative ability appears to be an intrinsic property of the material and the seemingly unique way it interacts with the host, once implanted. MAA based biomaterials generate vessel rich tissue (that integrates with the host) instead of a fibrous capsule that acts as a barrier. Using different co-monomers, the material is used as a coating for various medical devices (e.g., polypropylene mesh) to improve their biocompatibility or as an injectable gel that is initially liquid but gels in situ. Interestingly we also see increased nerve regeneration. The biological properties all appear to derive from the high negative charge associated with methacrylic acid. The focus here is on biomaterials development. Aim 1 is to combine the vascularizing activity of methacrylic acid with the ability of collagen to enable cell adhesion and migration, in the form of an injectable gel, that combines the vascularizing properties of MAA with the cell supportive character of collagen. Aim 2 is to develop an understanding of the physicochemical source of the biological activity of MAA by delineating the dynamics of the connection among material surface charge, the cell membrane potential. and the cell receptor distribution. MAA based materials appear to hyperpolarize cells (making the inside more negative than normal). Aim 3 is to design a material that engages with a cell receptor in a specific fashion. We ask whether materials can be designed to have a specific biological activity by starting with the protein structure of a receptor and through in silico analysis, identify small molecules that can be incorporated into novel polymers. The successful use of implantable medical devices (>$300 billion global industry; high growth rate; high potential for growth in Canada) is built on the biocompatibility of inert biomaterials such as silicone rubber and polypropylene, among other materials. But inert materials do not enable the next generation of medical devices because the normal foreign body response to the inert material is a barrier for some applications. Because it is biologically active without growth factors or cells, MAA is a novel biomaterial in this context. We seek to create novel forms of MAA, understand its mechanism of action and design yet others.

医疗保健中使用的材料和基于这些材料的器械会产生生物反应，对该反应的控制决定了器械的成功使用。我们将建立一套基于甲基丙烯酸（MAA）的材料，该材料具有独特的再生特性，特别是但不仅是在没有任何生物成分的情况下再生血管的能力。这种再生能力似乎是材料的内在属性，以及一旦植入后与宿主相互作用的看似独特的方式。 基于MAA的生物材料生成血管丰富的组织（与宿主整合），而不是充当屏障的纤维囊。使用不同的共聚单体，该材料用作各种医疗器械的涂层（例如，聚丙烯网）以改善它们的生物相容性，或者作为最初为液体但原位胶凝的可注射凝胶。有趣的是，我们还看到了神经再生的增加。生物学特性似乎都源自与甲基丙烯酸相关的高负电荷。这里的重点是生物材料的发展。目的1是将甲基丙烯酸的血管化活性与胶原蛋白使细胞粘附和迁移的能力以可注射凝胶的形式结合联合收割机，所述可注射凝胶将MAA的血管化性质与胶原蛋白的细胞支持特性结合。目的2是通过描述材料表面电荷、细胞膜电位之间的动态联系，了解MAA生物活性的物理化学来源。和细胞受体分布。MAA为基础的材料出现hyperplasia细胞（使内部更负比正常）。目标3是设计一种以特定方式与细胞受体结合的材料。我们询问是否可以通过从受体的蛋白质结构开始并通过计算机分析来设计材料以具有特定的生物活性，从而识别可以并入新型聚合物的小分子。 植入式医疗器械的成功使用（全球产业规模超过3000亿美元;增长率高;加拿大增长潜力大）是建立在惰性生物材料（如硅橡胶和聚丙烯等材料）的生物相容性基础上的。但是惰性材料不能用于下一代医疗器械，因为对惰性材料的正常异物反应是某些应用的障碍。因为它在没有生长因子或细胞的情况下具有生物活性，所以MAA是这种情况下的新型生物材料。我们寻求创造新形式的MAA，了解其作用机制并设计其他。