Biomimetic Polymers with Reversible Cell Adhesive and Cell Resistant Properties, Biological Evaluation, Structural Optimization and Physicochemical Characterization of Finely-Tuned Pairs of Zwitterionic Polymers for Controlled Cell Binding and Release

本项目的目的是对各种超支化两性离子聚合物的可逆生物粘附性能进行生物评价和结构优化。该项目的背景是最近发现，具有基于天然磷酸胆碱（PC）的生物膜的反向偶极子的聚合物-所谓的磷酸胆碱（CP）-表现出可逆的细胞粘附特性。CP聚合物的这些性质可能依赖于与脂质双层细胞膜的外小叶磷酰胆碱偶极的多价相互作用，并且可以通过添加PC改性的聚合物来逆转。因此，假定可逆的细胞结合性质也将用其它基于甜菜碱的两性离子基团如磺基甜菜碱或羧基甜菜碱观察到，所述甜菜碱具有与CP两性离子相同的互补电荷的连续排列。多价两性离子聚合物是使用仿生方法设计的，因此是有前途的生物相容性聚合物。在该项目中，将鉴定这些聚合物的不同集合，其显示通过一种化合物的受控细胞结合和通过添加具有反向偶极的互补化合物经由竞争性结合从细胞中触发释放。将通过体外细胞培养实验研究两性离子偶极子内阴离子性质的影响，并且将在结合强度、生物相容性和特别是细胞毒性方面对用于可逆细胞粘附的聚甜菜碱的匹配组进行结构优化。定义的低分子量的CP和PC聚合物的类似物将通过等温滴定量热法揭示这一特定的互补两性相互作用的热力学参数的整个集合。这有助于更好地理解多价偶极相互作用。此外，将评价用可变两性离子基团改性的硬核纳米颗粒的细胞结合性质，并与相应的软核两性离子聚合物的性能进行比较。因此，它的目的是更深入地了解这些化合物的多价相互作用的机制，这将有助于在未来的设计这样的化合物在生物医学领域的具体应用，其中需要定义的属性，如结合强度或细胞摄取。预期这些聚合物将具有多方面的应用，例如新型局部药物递送系统、组织工程基质或医疗和诊断装置的表面涂层材料。

The aim of this project is the biological evaluation and structural optimization of various hyperbranched zwitterionic polymers for their reversible bioadhesive properties. The background for this project is the recent finding that polymers that bear reversed dipoles of natural phosphorylcholine (PC) based biomembranes - so called choline phosphates (CP) - exhibit reversible cell adhesive properties. These properties of the CP polymer presumably rely on a multivalent interaction with the outer leaflet phoshorylcholine dipoles of the lipid bilayer cell membrane and can be reversed by addition of a PC modified polymer. It is therefore postulated that reversible cell binding properties will also be observed with other betaine based zwitterionic groups such as sulfobetains or carboxybetaines which have the same consecutive arrangement of complementary charges as the CP zwitterions. The multivalent zwitterionic polymers are designed using a biomimetic approach and are therefore promising biocompatible polymers. Within this project distinct sets of these polymers will be identified which show controlled cell binding by one compound and triggered release from the cell by addition of the complementary compound with the reversed dipole via a competitive binding. The influence of the nature of the anions within the zwitterionic dipoles will be studied by in vitro cell culture experiments and matching sets of polybetaines for reversible cell adhesion will be structurally optimized with respect to binding strength, biocompatibility and in particular cell toxicity. Defined low molecular weight analogues of CP and PC polymers will reveal the whole set of thermodynamic parameters of this particular complementary zwitterion interaction via isothermal titration calorimetry. This contributes to a better fundamental understanding of the multivalent dipol-interaction. In addition, hard core nanoparticles modified with variable zwitterionic groups will be evaluated for their cell binding properties and compared to the performance of the respective soft core zwitterionic polymers. Thereby, it is aimed at a deeper mechanistical understanding of the multivalent interaction of these compounds which will help in the future design of such compounds for specific applications in the biomedical field where defined properties such as binding strength or cell uptake are needed. It is expected that these polymers will have multi-facetted applications such as novel localized drug delivery systems, tissue engineering matrices or surface coating materials of medical and diagnostical devices.