Weak bond-based injectable and stimuli responsive hydrogels for biomedical applications

Abstract

Here we define hydrogels crosslinked by weak bonds as physical hydrogels. They possess unique features including reversible bonding, shear thinning and stimuli-responsiveness. Unlike covalently crosslinked hydrogels, physical hydrogels do not require triggers to initiate chemical reactions for in situ gelation. The drug can be fully loaded in a pre-formed hydrogel for delivery with minimal cargo leakage during injection. These benefits make physical hydrogels useful as delivery vehicles for applications in biomedical engineering. This review focuses on recent advances of physical hydrogels crosslinked by weak bonds: hydrogen bonds, ionic interactions, host-guest chemistry, hydrophobic interactions, coordination bonds and π-π stacking interactions. Understanding the principles and the state of the art of gels with these dynamic bonds may give rise to breakthroughs in many biomedical research areas including drug delivery and tissue engineering.

Phototransformative Supramolecular Assembly of Amphiphilic Diarylethenes Realized by a Combination of Photochromism and Lower Critical Solution Temperature Behavior

“…Not only the hydrophobic interaction, but also hydrogen bonding and metal coordination contribute to determining the structure . Among several directions of study, macroscopic transformation of the assembly in response to external stimuli is currently under intensive investigation …”

Anti‐Biofouling and Healable Materials: Preparation, Mechanisms, and Biomedical Applications

“…Injectable hydrogels are also promising materials for biomedical applications like drug delivery due to their biocompatibility, ease of operation, minimal invasion, and most importantly, similarity with natural extracellular matrices . For instance, the injectable hydrogels reported by Zeng and co‐workers were crosslinked by hydrogen bondings and aromatic interactions from catechol functional groups, which belonged to physical hydrogels and did not need any triggers for in situ gelation.…”

Synthesis and gelation of copolypept(o)ides with random and block structure

“…Hydrogels formed by water‐soluble macromolecular networks have witnessed rapid growth in biomedical application varying from contact lenses and wound dressing to implantable depots as drug carriers and scaffolds for tissue engineering . In particular, physical crosslinking driven by non‐covalent interactions like H‐bonding, ion attraction, hydrophobic force and host‐guest complexion has endowed the resulted hydrogel with rapid self‐adaptability and self‐assembly versatility in different environments . Inspired by living tissues, natural hydrogels like collagen, elastin, hyaluronic acid and sodium alginate have been extensively explored for cell immobilization and tissue regeneration .…”

“…[1,2] In particular, physical crosslinking driven by non-covalent interactions like H-bonding, ion attraction, hydrophobic force and host-guest complexion has endowed the resulted hydrogel with rapid self-adaptability and self-assembly versatility in different environments. [3,4] Inspired by living tissues, natural hydrogels like collagen, elastin, hyaluronic acid and sodium alginate have been extensively explored for cell immobilization and tissue regeneration. [5] However, most biomacromolecules are chemically complex and difficult to alter their properties for the clinical use.…”