Synthesis of Peptide-based Zwitterionic Cross-linkers and Evaluation in Bioadaptable Hydrogels

Regents Of The University Of Idaho, Moscow ID

Investigators

Abstract

Non-Technical Abstract: Polymers, which are composed of repeating units called monomers, are everywhere. Polymers that contain large amounts of water, like contact lenses, are called hydrogels. One use of hydrogels involves placing these materials into the body to help overcome a biological deficiency (injury, disease, impairment, etc.). The body’s response to these “biomaterials” is dependent upon the material properties - incompatible materials are rejected by the body. Similarly, the physical characteristics should match those of the original tissue. There is a need for more control over the biomaterials given this broad range of applications. The goal of this project is to create a new class of hydrogels that provide improved control of the material properties. This will be done through the creation of new charged, but neutral, amino acid-based molecules that hold the hydrogel together (cross-linkers). These species will react with other charged monomers creating three-dimensional hydrogel networks. Important hydrogel properties that will be investigated include the binding of biological species, the delivery of biological signals, the material physical properties, and the breakdown of the biomaterial over time. The material properties will be linked to the composition of the amino acid-based molecules. The result will be a library of new hydrogels with controlled properties for broad use. A series of experiments will also be created for professional development workshops with local high school teachers to bring this science to the classroom. Technical Abstract: There is a need for novel bioadaptable materials to address clinical challenges associated with biomedical therapies and other biological applications that use polymer-based materials. To be defined as bioadaptable, the material must meet four criteria: resistance to nonspecific protein adsorption, the ability to deliver specific biological signaling molecules (proteins, peptides, etc.), tunable mechanical properties, and tunable degradation behavior. Polyampholyte biomaterials show promise for being defined as bioadaptable because of their demonstrated nonfouling behavior, ability to deliver bioactive proteins, multiple approaches for controlling their mechanical properties, and tunable degradation behavior. However, a significant limitation to the advancement of these polymers is the lack of zwitterionic cross-linker molecules and a subsequent understanding of the cross-linker structure and physical property relationships that will guide their end use. The overall goal is to design and synthesize a library of peptide-based zwitterionic cross-linkers which will be incorporated into polyampholyte hydrogels to develop structure-property relationships between the cross-linker species and the resulting polymer hydrogels. This will lead to a fundamental understanding of design criteria for the cross-linker which in turn will facilitate development of bioadaptable biomaterial hydrogels. It is hypothesized that molecular-level control over the length, chemistry, charge spacing, charge density, and pendant side chain presentation will lead to the demonstration of bioadaptable polyampholyte hydrogels. This hypothesis will be tested by synthesizing peptide-based cross-linkers with controlled structure and incorporating these cross-linkers into polyampholyte hydrogels. Hydrogel performance metrics will be evaluated, resulting in a fundamental correlation of the structure-property relationships of polyampholyte hydrogel performance metrics to structural design features in the library of peptide-based zwitterionic cross-linkers. The award will provide course-based undergraduate research experiences (CUREs) for students at the University of Idaho. The team will also provide teacher workshops to broaden knowledge in the topic of hydrogels. This project is jointed funded by the Biomaterials (BMAT) program and the Established Program to Stimulate Competitive Research (EPSCoR). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.