N-Acetylcysteine Applied to Hydrogels: A Comprehensive Systematic Review

N-acetylcysteine (NAC) is a thiol-containing molecule with antioxidant, anti-inflammatory, antimicrobial, and cytoprotective properties that has increasingly been incorporated into hydrogel-based biomaterials. This systematic review evaluates the strategies used to integrate NAC into hydrogels and examines their effects on material properties, controlled release, biocompatibility, and therapeutic activity. The review was conducted according to the PRISMA guidelines using Scopus, PubMed, Web of Science, and SciFinder to identify English-language articles published between 2000 and 2025. Seventy-three studies met the eligibility criteria of this review. NAC has been employed as a physically loaded therapeutic agent, covalently conjugated polymer modifier, contributor to hydrogel crosslinking, metal-coordination ligand, and compound incorporated into nano- and microparticulate carriers dispersed in hydrogel. These approaches enable the modulation of gelation, swelling, adhesion, degradation, and drug-release kinetics. NAC-containing hydrogels have demonstrated robust antioxidant, antimicrobial, antibiofilm, anti-inflammatory, angiogenic, and tissue-regenerative properties in various in vitro and in vivo models, underscoring their potential for advanced biomaterial applications. Release profiles varied from rapid stimulus-responsive delivery to sustained release over several days, depending on the network architecture and the NAC-matrix interactions. However, comparisons among studies were limited by the heterogeneous formulations, release conditions, biological models, and outcome measures. Standardized physicochemical characterization, NAC stability assessment, dose-response evaluation, and rigorous preclinical validation are required to support the translation of NAC-based hydrogels into biomedical applications. We hope that this review will help scientists and innovation centers understand the potential of the NAC-containing hydrogel biomaterials discussed in this study, as well as the opportunities and demands for additional research in this field.