Polymeric Chemical and Physical Interfaces with Blood and Musculo-skeletal tissues

聚合物与血液和肌肉骨骼组织的化学和物理界面

• 批准号: RGPIN-2018-04424
• 负责人: Santerre, Paul
• 金额: $ 4.66万
• 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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=691270
• 关键词: Polymeric; Chemical; Physical; Interfaces; Blood

Polymeric materials are made of very large molecules that self assemble into materials that have practical applications. Polymers are now commonly used in the medical field for many applications including implants for orthopaedics, dental, and vascular devices, along with many others. While for the past 40 years, these polymers have been relatively simple in nature, consisting primarily of materials made of one (i.e. polyethylene) or possibly two (i.e. polyethylene terephthalate) building blocks called monomers, our research laboratory has been exploring more complex structures with four or five completely different monomer building blocks at a time, in order to reflect some of the complex heterogeneity seen in bio-polymers (the biological molecules that carry out most of the function in our body). Upon implantation into the body, one of the first things that happens is that polymers interact with bio-polymers called proteins. These proteins are natural polymers which often contain over 10 different monomers if not more, reflecting hydrophobic, hydrophilic and ionic function. Changes in the structure of proteins are often forced upon the bio-polymers by synthetic polymers that only have one or two monomer structures. This transformation occurs in order to minimize interfacial energy between the surface and proteins. These changes often lead to negative reactions that affect biocompatibility with the cells in tissues, including the foreign body cell reactions with extracellular proteins and other cells within the body; blood clotting activity involving proteins, blood platelets and white blood cells; interfacial bonding between mineralized and extracellular matrix proteins of soft tissues; and bacterial biofilm formation at the interface of biomaterials and the latter tissues. A perspective which remains understudied is how does one use the discovered knowledge of protein interactions with surfaces as “an analytical tool” for inspiring and directing innovative new heterogeneous material chemistry, and generating tailored physical features and/or microdomain structures with morphologies that can influence the above biological processes, such as to arrive at materials which correct the aforementioned problems. It is our desire in this Discovery grant to use our knowledge gained in free radical generated polyurethane chemistry, which affords the chemical diversity of block copolymers, the ability to phase separate to form intermolecular domain structures, and the versatility in processing to readily yield physical cues that influence cell function, to now drive a program on innovative new polymeric biomaterials development. This work will one day lead to new products, conceived by evolving Canadian entrepreneurs in the field, as has been shown possible by the Santerre lab for over two decades now.

聚合物材料是由非常大的分子自组装成具有实际应用的材料。聚合物现在通常用于医疗领域的许多应用，包括骨科、牙科和血管设备的植入物以及许多其他应用。在过去的40年里，这些聚合物的性质相对简单，主要由一种(即聚乙烯)或可能两种(即聚对苯二甲酸乙二酯)称为单体的构建块组成的材料组成，我们的研究实验室一直在探索更复杂的结构，一次使用四到五个完全不同的单体构建块，以反映生物聚合物(执行我们身体大部分功能的生物分子)中的一些复杂的异质性。在植入人体后，首先发生的事情之一是聚合物与称为蛋白质的生物聚合物相互作用。这些蛋白质是天然聚合物，通常含有10多种不同的单体，反映出疏水、亲水和离子功能。蛋白质结构的改变通常是由只有一个或两个单体结构的合成聚合物强加给生物聚合物的。这种转变的发生是为了使表面和蛋白质之间的界面能最小化。这些变化往往导致影响与组织内细胞生物相容性的负面反应，包括异物细胞与细胞外蛋白和体内其他细胞的反应；涉及蛋白质、血小板和白细胞的凝血活性；软组织矿化的细胞外基质蛋白之间的界面结合；以及生物材料和组织界面上细菌生物膜的形成。一个仍未得到充分研究的角度是，人们如何利用已发现的蛋白质与表面相互作用的知识作为“分析工具”，启发和指导创新的多相材料化学，并产生可影响上述生物过程的量身定制的物理特征和/或微域结构，例如获得纠正上述问题的材料。在这笔探索基金中，我们希望利用我们在自由基生成的聚氨酯化学中获得的知识，提供嵌段共聚物的化学多样性、相分离形成分子间结构的能力，以及加工过程中的多功能性，以便容易地产生影响细胞功能的物理线索，现在推动创新的新型聚合物生物材料开发计划。这项工作有朝一日将带来由该领域不断发展的加拿大企业家构思的新产品，桑特瑞实验室20多年来已经证明了这一点是可能的。