Designing Peptide/Graphene Hybrid Hydrogels through Fine-Tuning of Molecular Interactions.

Jacek K Wychowaniec,Alberto Saiani,Aline F Miller,Aravind Vijayaraghavan,Jonathan Moffat,Wagner A Pinheiro,Mohamed A Elsawy,Mi Zhou,Maria Iliut,Judith A Hoyland

doi:10.1021/acs.biomac.8b00333

Abstract

A recent strategy that has emerged for the design of increasingly functional hydrogels is the incorporation of nanofillers in order to exploit their specific properties to either modify the performance of the hydrogel or add functionality. The emergence of carbon nanomaterials in particular has provided great opportunity for the use of graphene derivatives (GDs) in biomedical applications. The key challenge when designing hybrid materials is the understanding of the molecular interactions between the matrix (peptide nanofibers) and the nanofiller (here GDs) and how these affect the final properties of the bulk material. For the purpose of this work, three gelling β-sheet-forming, self-assembling peptides with varying physiochemical properties and five GDs with varying surface chemistries were chosen to formulate novel hybrid hydrogels. First the peptide hydrogels and the GDs were characterized; subsequently, the molecular interaction between peptides nanofibers and GDs were probed before formulating and mechanically characterizing the hybrid hydrogels. We show how the interplay between electrostatic interactions, which can be attractive or repulsive, and hydrophobic (and π-π in the case of peptide containing phenylalanine) interactions, which are always attractive, play a key role on the final properties of the hybrid hydrogels. The shear modulus of the hydrid hydrogels is shown to be related to the strength of fiber adhesion to the flakes, the overall hydrophobicity of the peptides, as well as the type of fibrillar network formed. Finally, the cytotoxicity of the hybrid hydrogel formed at pH 6 was also investigated by encapsulating and culturing human mesemchymal stem cells (hMSC) over 14 days. This work clearly shows how interactions between peptides and GDs can be used to tailor the mechanical properties of the resulting hydrogels, allowing the incorporation of GD nanofillers in a controlled way and opening the possibility to exploit their intrinsic properties to design novel hybrid peptide hydrogels for biomedical applications.

Highlights

Progress in the cell culture and tissue engineering fields requires the design of novel functional biomaterials, in particular three-dimensional (3D) scaffolds.[1−4] Hydrogels, which are highly hydrated materials, have come to the forefront in the design of such scaffolds, which need to be biocompatible, mechanically tunable, and offer opportunity for biofunctionalization
It has been shown that these peptides form β-sheet rich fibers with the hydrophobic residues buried in the core, while the hydrophilic residues are located on the surface of the fibers (Figure 1C).[41−43] As a result, we have shown that the hydrophobic residues control the self-assembly into β-sheet fibers as well as the fibers intrinsic properties such as persistence length,[44] while the hydrophilic residues control fiber solubility, fiber−fiber interactions and network formation.[42]
Our results suggest that the effect of adding graphene derivatives (GDs) to these hydrogels is a balance between fiber sequestrations on the GDs surfaces and its detrimental effect on the overall network fiber and cross-link densities that will lead to lower G′ (F8 case) and the additional strong physical network cross-linking resulting from fibers adhering on the surface of GDs, which will contribute to the overall reinforcement of the mechanical properties of the network, leading to higher G′ (V8 case)

Summary

Introduction

Progress in the cell culture and tissue engineering fields requires the design of novel functional biomaterials, in particular three-dimensional (3D) scaffolds.[1−4] Hydrogels, which are highly hydrated materials, have come to the forefront in the design of such scaffolds, which need to be biocompatible, mechanically tunable, and offer opportunity for biofunctionalization. A variety of natural and synthetic molecular building blocks can be found in the literature that allows the design of such hydrogels. One such block, which has attracted significant interest in the past decade, is β-sheet forming peptides. This work provides new insight into how molecular interactions between peptide fibers and GDs affect the bulk properties of this family of peptide hydrogels, providing new design opportunities for the formulation of functional hybrid hydrogels with tailored properties

Methods

Results

Conclusion