Biocompatible polymer interactions with biological structures

我们最近描述了一种用于细胞的“万能胶”，基于我们令人惊讶的观察，用两性离子胆碱-磷酸（CP）基团装饰的超支化或线性聚合物与含有PC基团的细胞膜紧密结合，PC基团在自然界中无处不在。这一发现将导致许多生物医学应用，例如在手术中的血液停止和组织密封（止血），但由于合成CP基团的效率较低，该领域发展缓慢。我们的长期目标是开发一种基于这种或相关类型的生物粘附的新型止血材料，这种材料可以附着在组织边缘并通过聚集血细胞诱导堵塞。在近期，我们将合成一个家族的超支化聚甘油（HPGs）携带相关甜菜碱，已知在所有的情况下，除了CP的情况下，是排斥蛋白质和细胞，有或没有添加聚合为细胞结合提供粘接能量。这里的目标是(a)更好地理解CP与细胞结合但排斥蛋白质的异常现象，以及(b)开发基于甜菜碱保护的新型生物粘合剂，以防止通常有害的聚阳离子诱导的结合。我们最近研究了血液中的这种聚合物系统，并发现了复杂的凝血反应，例如，聚合物与红细胞和血小板结合引起激活和聚集，同时抑制部分凝血级联和凝块形成。我们计划在下一个资助期内大大扩展这类研究，以便能够更好地定制含有这些基团的聚合物的生物反应。

We recently described a ‘universal glue’ for cells based on our surprising observation that hyperbranched or linear polymers decorated with zwitterionic choline-phosphate (CP) groups bound strongly to cell membranes containing PC groups, which are ubiquitous in nature. This discovery should lead to numerous biomedical applications, for instance in blood arrest and tissue sealing (hemostasis) during surgery, but the field is evolving slowly because of low efficiencies in synthesizing CP groups. Our long term goal is to develop a new category of hemostatic materials based on this or related types of bioadhesion that would attach to tissue margins and induce plugging by aggregating blood cells. In the near term we will synthesize a family of hyperbranched polyglycerols (HPGs) carrying related betaines, known in all but the CP case to be repulsive to proteins and cells, with and without added polycations to provide adhesive energy for cell binding. The goal here is (a) to better understand the anomaly of CP binding to cells but rejecting proteins, and (b) to develop new bioadhesives based on betaine protection against normally damaging polycation-induced binding. We have recently studied such a polymer system in blood and have found complex coagulation responses, for instance, with the polymers binding to red cells and platelets causing activation and aggregation while inhibiting parts of the coagulation cascade and clot formation. We plan to greatly expand such studies in the next funding period to be able to better tailor the biological response to polymers bearing these groups.