Low-molecular-weight hydrogels: Synthetic methodologies, gelation mechanisms, and biomedical applications

Low-molecular-weight hydrogels (LMWHs) have garnered widespread focus as versatile soft materials owing to their distinctive characteristics and potential applications. LMWHs are synthesized from small molecules that, upon assembly, form entangled aggregates via different types of noncovalent interactions, such as hydrogen bonding, van der Waals forces, or π-π stacking interactions. LMWHs are characterized by their unique ability to mimic biological systems by effectively absorbing and retaining large quantities of water. Despite their poor mechanical properties, LMWHs are widely used in various medical applications due to their easy preparation, biocompatibility, and low toxicity. Smart LMWHs demonstrate responsiveness to external stimuli, such as light, temperature, enzymes, or pH, rendering them ideally adapted for various controlled drug delivery applications. LMWHs have been extensively employed in different biomedical applications, including drug delivery, tissue engineering and cell culture, wound healing, and biofabrication. In this chapter, we aim to explore the potential of LMWHs as drug-delivery vehicles for a range of medications, focusing on the different synthetic strategies, gelation processes, and drug-loading and releasing mechanisms.