Elsevier

Polymer

Volume 139, 14 March 2018, Pages 86-97
Polymer

Nanocomposite hydrogels based on agarose and diphenylalanine

https://doi.org/10.1016/j.polymer.2018.02.007Get rights and content

Highlights

  • Self-assembly of agarose and diphenylalanine led to nanocomposite hydrogels.

  • Diphenylalanine nanowires embedded agarose network effectively reinforced hydrogels.

  • Dehydration-derived toughening behavior was observed for the nanocomposite gels.

  • Dehydrated and compressed composite gels re-swelled to recover their original shape.

Abstract

Nanocomposite hydrogels were prepared by temperature-induced self-assembly of agarose and diphenylalanine (FF) mixtures in water. We investigated the mechanical and thermal properties, and the structure of agarose/FF composite systems. The FF assembly was significantly influenced by the existence of agarose molecules, which formed relatively thin FF nanowires (NWs) (microwires form from pure FF solutions) passing through meshes of agarose networks. The storage and compressive moduli of the nanocomposite gels significantly increased by increasing the FF content (up to 2 wt% for a 1 wt% agarose matrix). The nanocomposite gels did not fracture, even at a strain of 95%, but contracted uniformly by expelling most of the water during a compressive deformation. The highly compressed gels re-swelled in water and slowly recovered their original cylindrical monolithic shape. The unusual viscoelastic and compressive behaviors of nanocomposite gels is attributed to the unique nanostructure of interpenetrating networks between rigid NWs and the agarose matrix. Osteoblast-like cells (MG63) cultured on the nanocomposite hydrogels demonstrated that the FF assemblies could improve the cell viability of the agarose gel.

Graphical abstract

The diphenylalanine (FF) assembly was significantly influenced by the gelling of agarose, which formed relatively thin FF nanowires (microwires form from pure FF solutions) passing through meshes of agarose networks.

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Introduction

Agarose is a polysaccharide extracted from the cell walls of marine red algae as a sub-fraction of agar; it is used for its gelling properties in the food industry and medical applications for tissue-engineering [[1], [2], [3], [4], [5]]. In a hot solution state at approximately 95 °C, agarose chains exist in a randomly coiled configuration. Upon cooling below approximately 40 °C, the coils order to form helices that further aggregate into thick bundles called super helices, leading to a three-dimensional network [[6], [7], [8], [9], [10], [11]]. Hydrogels that consist of three-dimensional networks and a large amount of water (>90%) have been widely used in medical applications, such as drug-delivery systems and tissue engineering [[1], [2], [3]]. However, most hydrogels fracture easily, even under mild loading conditions, because of their poor mechanical strength and toughness [12]. Efforts to overcome these mechanical challenges include designing composite hydrogels using stiff fillers to stabilize the network structures [12,13]. Agarose composite hydrogels have been extensively investigated using hyaluronic acid, xanthan, carbon fibers, carbon nanotubes, nano-clays, and cellulose nanowhiskers as fillers [[14], [15], [16], [17], [18], [19], [20], [21]]. Diphenylalanine (NH2-Phe-Phe-COOH, FF) molecules, the core motif of the β-amyloid polypeptide, form tubes, spheres, vesicles, flowers, fibers, rods, and wires [[22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34]]. The polymorphism of the FF assembly can be easily controlled based on the experimental conditions, e.g., solvents, substrates, FF concentrations, pH, and temperature [[26], [27], [28], [29], [30], [31], [32], [33], [34]]. These FF assemblies present excellent mechanical properties, for example, a high Young's modulus of ∼20 GPa and point stiffness of 160 N/m for nanotubes, which are much higher than the properties of other biological materials [[35], [36], [37]]. In spite of their excellent mechanical properties, the application of FF assemblies as fillers has not been studied in reinforcing hydrogels. FF assemblies are good biodegradable materials, unlike typical inorganic fillers (e.g., carbon nanotubes); therefore, they should be ideal fillers for reinforcing the agarose hydrogel matrix without compromising the biodegradability and biocompatibility. In this paper, reinforced nanocomposite gels were prepared through a temperature-induced self-assembly of agarose and FF mixtures in water. The large wires/tubes (thickness on the order of micrometers) were formed from the pure FF solutions. However, for the composite gels, FF molecules assembled into much thinner nanowires (NWs) and passed through the meshes of the agarose network. The presence of gelling agarose significantly influenced the FF assembly. The structure, mechanical and thermal properties, and cell viability of the resultant nanocomposite hydrogels were investigated as a function of the FF concentration and compared with pure agarose gels.

Section snippets

Materials

Agarose powders were purchased from Sigma-Aldrich (product number: A0576). According to the agarose characteristics provided by the supplier, the sulfate content is less than 0.12%, and the melting temperature is approximately 86 °C. The FF peptides were purchased from Bachem (Bubendorf, Switzerland) and used as received.

Preparation of FF self-assemblies and agarose/FF composite hydrogels

The pure agarose hydrogels were prepared by dissolving agarose powder in hot water (95 °C) and cooling the solutions to room temperature without any disturbance. The FF was

SEM measurements

The formation of large tubes or wires by reducing the temperature of the hot FF aqueous solutions has been previously reported [[32], [33], [34]]. The thermally reversible self-assembly of FF in water was investigated as a function of ϕFF. The temperature-dependent self-assembly of FF molecules was monitored by visual inspection. The FF solution with ϕFF = 0.2 wt% remains transparent upon cooling to 25 °C, but slowly changes to a white solution after 12 h. However, solutions with higher

Conclusions

SEM analysis showed that FF could form rigid NWs passing through the meshes (pores) of the agarose network. An FF concentration of 0.5 wt% was the critical concentration to form NWs to reinforce the 1% agarose network. Fitting the SANS data with two Lorentzian models indicated that 0.5 wt% FF formed stiff assemblies in the agarose solutions at 75 °C. The NWs in the composite gel at 25 °C were 200–300 nm thick, as determined by the SEM results, which agreed with the SANS analysis. Significant

Acknowledgements

For financial support of this research, we thank the International Collaborative Research and Development Program (N0001230) funded by the Ministry of Trade, Industry & Energy of Korea.

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