Engineering biocompatible chitosan hydrogels with polyether-based crosslinkers for biomedical applications

Chitosan is a biocompatible and biodegradable biopolymer widely used in biomedical applications. The design of chitosan-based hydrogels with tunable physicochemical and mechanical properties is essential to adapt their performance to specific therapeutic requirements. In this work, a series of chitosan-based hydrogels (HGs) were synthesized via thiol-ene click chemistry using various crosslinkers, including linear polyethylene glycol (PEG), dendritic polyglycerol (dPG), and nanogels (NGs), to develop biomaterials with tunable physicochemical and mechanical properties for biomedical applications. Carboxymethyl chitosan was functionalized with thiol groups and crosslinked with the acrylated crosslinkers. The resulting HGs were comprehensively characterized by nuclear magnetic resonance, scanning electron microscopy, water absorption studies, and rheological measurements to assess their chemical composition, morphology, water absorption capacity, and mechanical behavior, respectively. The morphology and swelling behavior of the materials varied depending on the type, degree of acrylation, and concentration of the crosslinker. Linear PEG produces HGs with enhanced water absorption capacity and higher storage moduli due to its flexible structure, while HGs prepared with dPG exhibited reduced water absorption and a broader range of mechanical properties. HGs incorporating nanogels formed softer networks with intermediate water absorption capacity, showing lower gelation efficiency. Rheological analysis demonstrated that the storage modulus of the hydrogels could be tailored for applications ranging from soft tissue scaffolds to injectable drug delivery systems. In vitro cytocompatibility assays with human fibroblasts and keratinocytes confirmed that all HG formulations were not cytotoxic. These findings highlight the potential of these HGs as versatile platforms for regenerative medicine and controlled drug delivery.