Chitosan nanocrystals as next-generation antimicrobials: Mechanistic insights, antibiotic synergy, and biomedical...

Chitosan, derived from crustacean and fungal chitin, is a versatile biopolymer with broad-spectrum antimicrobial activity governed by its molecular weight, degree of deacetylation, and crystallinity. Nanoscale derivatives, especially chitosan nanocrystals (ChNCs) and chitosan-based nanocomposites, exhibit enhanced efficacy through increased surface area, stronger electrostatic interactions, improved biofilm penetration, and metal-ion chelation. ChNCs also act synergistically with multiple antibiotic classes, restoring potency against multidrug-resistant pathogens, while chemical modification further expands their antimicrobial potential. Beyond antimicrobial use, chitosan and ChNCs are increasingly integrated into implantable devices, including orthopedic coatings, dental membranes, and guided bone regeneration scaffolds, where their bioactivity and degradability support osseointegration and localized therapeutic delivery. Although nanoforms may show higher cytotoxicity, they remain biocompatible within therapeutic ranges when properly engineered. Chitosan, ChNCs, and their nanocomposites/derivatives represent sustainable, modular platforms for next-generation antimicrobial and biomedical technologies. Emerging directions include green synthesis, metal-functionalized hybrids, and AI-assisted optimization to achieve predictable, tunable biological performance and accelerate clinical translation.