Biomaterials by design

医疗保健中使用的材料和基于这些材料的设备会产生生物反应，对这种反应的控制决定了设备的成功使用。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性能，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这种材料的一种内在属性，以及一旦被植入，它与宿主相互作用的似乎独特的方式。 基于MAA的生物材料产生丰富的血管组织(与宿主整合)，而不是充当屏障的纤维胶囊。使用不同的共聚单体，该材料可用作各种医疗设备(如聚丙烯网状物)的涂层，以提高其生物相容性，或用作可注射凝胶，最初为液体，但可原位凝胶。有趣的是，我们还看到神经再生增加。这些生物特性似乎都来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开发。目的1是以注射凝胶的形式，结合甲基丙烯酸的血管形成活性和胶原的细胞黏附和迁移能力，将MAA的血管形成特性和胶原的细胞支持特性结合在一起。目的2是通过描绘材料表面电荷和细胞膜电位之间的联系的动力学，加深对MAA生物活性的物理化学来源的理解。以及细胞受体的分布。以MAA为基础的材料似乎会使细胞超极化(使内部比正常情况下更负面)。目标3是设计一种以特定方式与细胞受体结合的材料。我们问，是否可以从受体的蛋白质结构开始，通过电子分析，识别可以并入到新型聚合物中的小分子，从而设计出具有特定生物活性的材料。 植入式医疗设备的成功使用(全球行业价值3000亿美元；高增长率；加拿大的增长潜力很大)建立在硅橡胶和聚丙烯等惰性生物材料的生物相容性基础上。但惰性材料不能使下一代医疗设备成为可能，因为对惰性材料的正常异物反应是某些应用的障碍。由于MAA在没有生长因子或细胞的情况下具有生物活性，因此在这方面是一种新型的生物材料。我们寻求创造新的MAA形式，了解其作用机制，并设计其他形式的MAA。

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.