(325f) Synthesis and Evaluation of Zwitterionic Peptide-Based Cross-Linkers for Nonfouling Hydrogel Applications

Polyampholyte hydrogels are attractive materials for biomedical applications as they offer a wide variety of features including nonfouling, selective protein delivery, and tunable physical characteristics. Of these features, the nonfouling behavior of polyampholyte hydrogels sets them apart from many other biocompatible polymer systems. However, the nonfouling performance of these hydrogels are limited by the currently available cross-linker species. To address this shortcoming, a strategy for synthesizing peptide-based cross-linkers via a convergent coupling approach is presented. This strategy has been used to synthesize a growing family of zwitterionic cross-linkers using peptides as the key building blocks. Specific examples of this family include N-Ser-Ser-C dimethacrylate, N-Lys-Lys-C dimethacrylate, and N-Ser-Gly-Ser-C dimethacrylate to name a few.

These zwitterionic cross-linkers have been incorporated into polyampholyte hydrogels and their physical properties and biocompatibility were compared against polyampholyte hydrogels synthesized with ethylene glycol-based cross-linkers. The physical characteristics of the hydrogels were indistinguishable from each other regardless of the cross-linker species. However, the zwitterionic cross-linked hydrogels demonstrated excellent nonfouling performance, while promoting enhanced cellular adhesion to fibrinogen delivered from the hydrogel. The results suggest that the zwitterionic cross-linkers enhance the performance of polyampholyte hydrogels relative to ethylene glycol-based cross-linkers.

Finally, on-going efforts to sensitively quantify differences in nonfouling performance between the different zwitterionic cross-linkers will be discussed. These evaluations are being completed for thin film hydrogels using a surface plasmon resonance biosensor. The objective is to identify the impacts of subtle structural differences between the zwitterionic cross-linkers on their subsequent nonfouling performance.