Nonswellable and Tough Supramolecular Hydrogel Based on Strong Micelle Cross-Linkings

Abstract

Because of the difference in osmotic pressure, most tough hydrogels swell under physiological conditions, which seriously weakens their mechanical properties, limiting their applications in biomedicine. Herein, a novel strategy based on strong and high-density micelle cross-linkings is proposed to prepare nonswellable and tough hydrogel. To realize a strong micelle cross-linker, the synergetic effect of hydrophobic and quadruple hydrogen-bonding interactions is employed by introducing an alkyl chain-protected ureido pyrimidinone moiety into a segmented copolymer backbone. The length of the alkyl is the key factor in determining the strength of the hydrophobic interaction, which was carefully tailored to gain micelles with high strength and suitable solubility. A supramolecular hydrogel was formed in situ by simply linking micelle cross-linkers with poly(ethylene glycol) chains. The strong and high-density micelle cross-linkings restrain multiple effective chains outside the micelle from stretching during swelling, and the deformability of micelle cross-linkings disperses the local stress to maintain the network with high cross-linking density upon loading. Therefore, the hydrogel exhibited an outstanding nonswelling behavior under physiological conditions and excellent mechanical properties with a compressive strength of 4 MPa. The rapid in situ gelation also facilitated injection and cell encapsulation. Meanwhile, it also showed good tissue adhesion, cytocompatibility, and suitable degradability. This novel and facile strategy can offer new insights into the exploitation of cross-linkings to prepare nonswellable hydrogels for biomedical applications.

Facile fabrication of tough and biocompatible hydrogels from polyvinyl alcohol and agarose

“…For instance, the tensile strength of the swollen polyacrylamide gel was only 0.004 MPa 82 . Moreover, the strength‐retention ratio was higher than most anti‐swelling hydrogels in literatures (~30%) 34–38 . Considering that the majority of tissue was composed of water, the ability of hydrogels to retain their original shapes and mechanical performance in physiological environments were crucial for load‐bearing materials.…”

“…However, most tough hydrogels expand significantly in water 3,4,14 . Obvious swelling not only weakens their mechanical behaviors but also damages adjacent cells and tissues 34,35 . Numerous effort has been made to address this issue whereas sophisticated recipes might retard their applications 34–38 .…”

“…At a specific molar ratio, the swelling issue was compensated by the thermo‐shrinking segments 34 . Additionally, compared with human tissues (skin or muscle), most non‐swellable gels are relatively weak 34–38 . Therefore, it is of great significance to prepare hydrogels which simultaneously display high strength, anti‐swelling property and excellent biocompatibility.…”

The Overview of Porous, Bioactive Scaffolds as Instructive Biomaterials for Tissue Regeneration and Their Clinical Translation

“…Moreover, supramolecular hydrogels such as self-assembled peptides (SAP)-based hydrogels can be formed enzymatically [ 70 ] or spontaneously depending on the initial peptide sequence chosen [ 71 ] whilst viscoelasticity can be introduced through non-covalent bonds [ 72 ]. Recently, a hydrogel with high mechanical properties a non-swelling behavior that allowed cell proliferation was obtained from crosslinking of micelles at high density [ 73 ]. Mechanical properties of hydrogels are also straightforward to handle, through initial monomer concentration [ 74 ] or via the crosslinking density [ 75 ].…”

Advanced Methods for the Characterization of Supramolecular Hydrogels

“…In general, TEM is used to obtain high-resolution images of hydrogels. At this resolution, it becomes possible to observe fundamental properties of the hydrogel, including the size of individual components, such as fibrils or micelles, forming the hydrogel or their distribution in the hydrogel [42,[69][70][71]. A comparison of hydrogels in different states is also useful.…”