Tuning Cross-Link Density in a Physical Hydrogel by Supramolecular Self-Sorting

Abstract

Cross-link density is an important parameter for the macroscopic mechanical properties of hydrogels. Increasing network density leads to an increase in the storage and loss moduli of the gel and can be accomplished by either increasing the concentration of cross-linkers, or by reducing the fraction of mechanically inactive cross-links. Mechanically inactive crosslinks consist of loops in the network, which do not contribute to the mechanical properties. Suppression of loop formation is demonstrated in a system of semiflexible supramolecular rods of poly(ethylene glycol)−bis(urea) bolaamphiphiles. Use of a cross-linker which, due to self-sorting of its hydrophobic segments, preferentially connects different rods, increases the modulus of a hydrogel by a factor of 15 compared to a system without self-sorting. By using statistical-mechanical calculations, it is shown that this increase can be explained by the increased tendency of the cross-linkers to form bridges between the semiflexible rods and thus increasing the cross-link density in the supramolecular hydrogel. ■ INTRODUCTIONHydrogels are cross-linked materials that absorb a substantial amount of water. They are of enormous economical importance due to their use as food additives, in the oil industry, and for biomedical applications. 1−3 In all applications, their mechanical behavior is of paramount importance, and it is determined to a large extent by cross-link density. In physical hydrogels, the cross-links are reversible, and control over mechanical behavior can be obtained by tuning chemical structure to create well-defined and specific cross-linking interactions. Cross-links are formed by specific parts of the components through aggregation by noncovalent interactions, such as ion complexation and hydrophobic interactions. 4 Specificity and additional strength of aggregation may be obtained by additional physical interactions such as hydrogen bonding. The combination of multiple noncovalent interactions gives highly desirable mechanical properties to natural hydrogelators such as collagen or actin. 5,6 The recent realization that mechanical properties and forces play an important role in the behavior of cells has opened up new markets for materials with tunable mechanical properties, with considerable potential for use in, for instance, tissue engineering. Despite their attractive mechanical properties, the use of natural hydrogelators in biomedical applications is limited by biocompatibility issues. With the aim of gaining full control over properties of biocompatible hydrogels, several synthetic approaches to physical hydrogels have been reported. Amino acids are popular building blocks in synthetic hydrogelators, both in engineered polypeptides 7 and synthetic peptide amphiphiles 8 because the chemical diversity of amino acids allows tuning of hydrophobicity and creates the possibility to engineer specific recognition motifs. Alternatively, hydrogelators have been developed with biocompatible poly(ethylene oxide) (PEO) as hydrophilic component and pep...

Controlling supramolecular polymerization through multicomponent self‐assembly

“…Strategies to control the size and shape of nano-and micrometer size objects that rely on selective solvent techniques in the self-assembly of block copolymers will not be discussed here. [60][61][62][63][64][65][66][67][68][69][70][71][72][73] Supramolecular multicomponent gels, [74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89] or orthogonal self-assembly, [90][91][92][93][94][95][96][97] self-sorting [98][99][100][101][102][103][104] and chiral amplification strategies 105 in multicomponent supramolecular polymers will not be covered in detail, and the interested reader is referred to the recent literature and review articles.…”

Crosslinker‐Induced Effects on the Gelation Pathway of a Low Molecular Weight Hydrogel

“…[36] A comparison of the hydrazone-forming reaction between gelator components at pH 5 and 7 showed distinct changes in the mechanical properties of the network consistent with differences in the hydrogel microstructure, thus demonstrating the importance of reaction rate on this process. [7,[10][11][12][13][14][15] Commonly, the addition of polymeric crosslinkers results in an improvement of the material's mechanical properties; however, competition between intraand interfibrillar crosslinking can occur preventing them from reaching their full mechanical potential. We became thus interested in studying the effect of various (bio)polymeric crosslinkers on the selfassembly process of this reaction-coupled hydrazide-aldehyde gelator into hydrogel materials as a model system (Scheme 1).…”

Supramolecular hydrogels: synthesis, properties and their biomedical applications

“…61 Currently, several strategies to improve hydrogel toughness have been introduced, such as the addition of chemical crosslinkers to provide permanent cross-linked networks, the combined use of multiple noncovalent interactions to enhance the cooperative effect between the cross-linkages, and the introduction of inorganic nanomaterials to produce organicinorganic hybrid cross-linked structures. In contrast, the 3D noncovalent crosslinked networks of supramolecular hydrogels show unique mechanical properties, including both stiffness/toughness and elasticity/flexibility to retain the hydrogel structure.…”