Enhancing the Stability of Hydrogels by Doubling the Schiff Base Linkages

Abstract

Schiff base bonds formed by primary amines and aldehydes are attractive for the construction of self‐healing and injectable hydrogels. However, biomedical applications of the Schiff base–based (SB) hydrogels are usually limited by their inherent low stability due to the rapid exchange dynamic of the Schiff base bond under physiological condition. Herein, a general method to improve the stability of SB hydrogels by simply doubling the Schiff base linkages at the cross‐linking points is proposed. The hydrogels formed by single Schiff base linkage (hydrogel I) disorganize into nano‐aggregates due to the rapid exchange dynamic of Schiff base bond, while the hydrogels formed by double Schiff base linkage (hydrogel II) maintain the gel network for longer times due to the improved stability of the double Schiff base linkage at cross‐linking points. Moreover, the hydrogel II displays excellent self‐healing and injectable properties due to the rapid dynamic nature of Schiff base bonds.

Relationship between Structure and Rheology of Hydrogels for Various Applications

“…Another method of synthesizing crosslinked hydrogels is through the formation of a Schiff base that is typically formed between amine and aldehyde groups [ 59 , 60 , 61 ]. The reaction between these groups forms an imine linkage that possesses an ability to uncouple and couple, creating self-healing characteristics [ 59 , 62 ].…”

Dynamic Tannic Acid Hydrogel with Self‐Healing and pH Sensitivity for Controlled Release

“…Under a large strain, the hydrogen bonds of FLaT hydrogels are destroyed, and the Schiff bases are partially broken; under a small strain, the physical interactions are rapidly rebuilt, and the Schiff bases are gradually restored. [ 17 ] Among the hydrogels, FLaT‐1 G ′ recovered the fastest. The recovered G ′ value of FLaT‐2 hydrogel was closer to the initial G ′ value because of its large amount of Schiff base bonds.…”

“…Schiff base refers to the reversible carbon–nitrogen double bonds formed by the reaction of carbonyl compounds (aldehydes or ketones) with primary amines or α ‐effect amines (alkoxyamines or hydrazines). [ 17 ] The reaction conditions of Schiff bases are mild and do not require external stimulation. Therefore, extensive research has been conducted on Schiff base‐based hydrogels, including chitosan, [ 18 ] peptides, [ 19 ] dextran, [ 17,20 ] and other amino‐rich natural polymers as the matrix.…”

“…[ 17 ] The reaction conditions of Schiff bases are mild and do not require external stimulation. Therefore, extensive research has been conducted on Schiff base‐based hydrogels, including chitosan, [ 18 ] peptides, [ 19 ] dextran, [ 17,20 ] and other amino‐rich natural polymers as the matrix. In addition, these Schiff base‐based hydrogels are sensitive to many chemical and biological stimuli, [ 21 ] such as pH, making them suitable for adjustable multiresponse hydrogel systems.…”

A chitosan-based multifunctional hydrogel containing in situ rapidly bioreduced silver nanoparticles for accelerating infected wound healing

“…13 However, Schiff base hydrogels usually possess the characteristics of poor stability and rapid degradation because of the hydrolysis sensitivity and the reversibility of the Schiff base reaction. 10,14,15 Recently, many researchers have overcome this shortcoming by constructing interpenetrating network (IPN) hydrogels using various cross-linking methods. 10,11,16 Photo-crosslinking is used to generate a rapid and stable cross-linking network, but such hydrogels are unable to recover from the deformations.…”