Biocompatible polymer interactions with biological structures

我们最近描述了一种用于细胞的“通用胶”，这是基于我们令人惊讶的观察结果，即用两性离子胆碱-磷酸(CP)基团装饰的超支化或线性聚合物强烈结合到含有PC基团的细胞膜上，PC基团在自然界中普遍存在。这一发现将导致大量的生物医学应用，例如在手术中的止血和组织封闭(止血)，但由于合成CP基团的效率较低，该领域进展缓慢。我们的长期目标是开发一种基于这种或相关类型的生物黏附的新型止血材料，这种黏附将附着在组织边缘，并通过聚集血细胞来诱导堵塞。在短期内，我们将合成一系列超支化聚甘油(HPG)，它们携带相关的甜菜碱，已知在所有情况下，除了CP案例外，对蛋白质和细胞都是排斥的，添加和不添加聚阳离子为细胞结合提供粘附能。这里的目标是(A)更好地了解CP与细胞结合但拒绝蛋白质的异常，以及(B)开发基于甜菜碱保护的新生物粘合剂，以防止通常破坏性的聚阳离子诱导结合。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导致激活和聚集，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大幅扩大这类研究，以便能够更好地定制对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.