Hydrogels Based on Schiff Base Linkages for Biomedical Applications

Abstract

Schiff base, an important family of reaction in click chemistry, has received significant attention in the formation of self-healing hydrogels in recent years. Schiff base reversibly reacts even in mild conditions, which allows hydrogels with self-healing ability to recover their structures and functions after damages. Moreover, pH-sensitivity of the Schiff base offers the hydrogels response to biologically relevant stimuli. Different types of Schiff base can provide the hydrogels with tunable mechanical properties and chemical stabilities. In this review, we summarized the design and preparation of hydrogels based on various types of Schiff base linkages, as well as the biomedical applications of hydrogels in drug delivery, tissue regeneration, wound healing, tissue adhesives, bioprinting, and biosensors.

Tailoring Gelation Mechanisms for Advanced Hydrogel Applications

“…[12] Examples include copper-catalyzed [13] or strain-promoted [14] azide-alkyne cycloadditions, Michael addition of Michael donors and acceptors, [15] thiolene reactions, [16] Diels-Alder [4 + 2] cycloaddition reactions, [17] disulfide bond formation, [18] and hydrazone or oxime bond formation. [19] Covalent crosslinking has also been investigated as a route to form polymer-nanoparticle hydrogels. For example, viscoelastic hydrogels have been formed via a Michael-type addition reaction between thiol-functionalized PEG chains and liposomes bearing maleimide [20] or acryloyl groups.…”

“…Michael addition [15,70,71] Thiol-ene addition [16,68,69] Diels-Alder [4 + 2 ] cycloaddition [17,[59][60][61] Inverse-electron demand Diels-Alder cycloaddition [2,[62][63][64][65][66] Disulphide bond formation [18] Hydrazone bond formation [19] -Free-radical polymerization [137][138][139][140][141][142][143] -Polyphenol-based reactions [95][96][97][98][99][100][101] Reactions between polymer chains and nanoparticles -Thiol-ene addition [20,21] -Free-radical polymerization [22] -EDC coupling [23] -Coordinate covalent bond formation [84] Electrostatic interactions Ion-polymer interactions [24][25][26][27][28][29] Polymer-polymer interactions [31,32] Other noncovalent interactions Polymer-polymer interactions [33,…”

“…[71] Other "click" reaction mechanisms which have been explored for hydrogelation include disulfide bond formation [18] and hydrazone or oxime bond formation. [19] Noncovalent interactions can also be used for hydrogel crosslinking. For example, the addition of ions can be used to form electrostatic interactions between polymer chains (e.g., calciumalginate hydrogels).…”

Emulating Human Tissues and Organs: A Bioprinting Perspective Toward Personalized Medicine

“…Imines are obtained from the reaction of aldehydes and amines, while the hydrazones and oximes are obtained from the reaction of aldehydes with hydrazides and hydroxyalamines. 229 These are dynamic bonds, meaning that they are reversible and in constant equilibrium between the bound and unbound state, while having significant higher strengths than physical bonds. Hydrogels based on such type of cross-linking are characterized by their good injectability, shear-thinning, and self-healing properties.…”

A Biocompatible, Stimuli-Responsive, and Injectable Hydrogel with Triple Dynamic Bonds

“…OSA functionalized with aldehyde groups cross-linked CMC with amine to form imine bonds via Schiff base reaction. Schiff base linkages are able to form under mild environments with a high reaction rate, which are ideal to prepare biologically relevant hydrogels [33]. Besides, dynamic acylhydrazone covalent bonds were also obtained by the reaction between aldehyde groups of OSA and hydrazide groups of DTP.…”