Incorporation of imidazolium chitosan derivative yields scaffolds with enhanced antioxidant, antimicrobial and immunomodulatory properties.

Developing biocompatible scaffolds with physicochemical properties suitable for regenerative medicine that also support cell adhesion and proliferation, while reducing local oxidative stress, exhibiting low immunogenicity and antimicrobial properties, represents a key objective in tissue engineering. Chitosan (CS), a biocompatible and biodegradable biopolymer, has attracted considerable attention in recent years as in tissue engineering. Herein, CS scaffolds were functionalized with bioactive antioxidant/antimicrobial molecules and reinforced with natural fillers to enhance these critical properties. The incorporation of a CS derivative containing 1-methylimidazole into CS-based scaffolds, and chitin nanowhiskers as reinforcement, was investigated. The resulting scaffolds exhibited an interconnected porous structure, facilitating nutrient diffusion and cell infiltration. Rheological analysis confirmed a predominantly soft and elastic behavior. Additionally, the antioxidant activity of the scaffolds was evaluated using the DPPH assay, while its antimicrobial effects were confirmed through bacterial inhibition tests. Fibroblast proliferation assays revealed an initial rapid growth phase followed by a stabilization. Immunological studies using macrophages demonstrated an initial activation of the NFκB transcription factor that did not result in the secretion of the pro-inflammatory cytokine IL-6, suggesting a transient macrophage activation. These findings highlight the potential of these CS-based scaffolds for biomedical applications by balancing structural integrity, cell compatibility and controlled immune response.