Emerging trends in polysaccharide-based smart PEGylated hydrogels for biomedical applications

Polysaccharide-based PEGylated hydrogels have emerged as multifunctional biomaterials that combine the favourable properties of polyethylene glycol (PEG), such as hydrophilicity, stability, and structural tunability with the biodegradability and biocompatibility of natural polysaccharides. This review presents recent progress in the synthesis and design of hybrid PEG-polysaccharide hydrogels, emphasizing structural modifications and crosslinking strategies involving biopolymers such as hyaluronic acid, alginate, chitosan, agarose, and carrageenan. These systems exhibit adjustable physicochemical properties and responsiveness to various stimuli, including temperature, light, pH, reactive oxygen species, glucose, and enzymatic activities. Such dynamic features enable precise control over drug and growth factor release and facilitate cell adhesion, proliferation, and tissue regeneration. The review also discusses the biomedical applications of these hydrogels in cancer therapy, wound healing, and tissue engineering. Furthermore, it highlights critical translational challenges related to biosafety, immunogenicity, large-scale production, and regulatory pathways, which still hinder clinical implementation. By integrating material design insights with translational perspectives, this work provides an updated overview of opportunities and limitations in advancing PEGylated polysaccharide hydrogels toward safe and effective biomedical use. Continued research on their stability, reproducibility, and functional performance is essential to unlock their full clinical potential.