**Background:** Chitosan, a cationic polysaccharide derived from chitin deacetylation, is a promising biomaterial for drug delivery and biomedical applications due to its biocompatibility, biodegradability, mucoadhesiveness, and antimicrobial properties. This review provides a comprehensive overview of chitosan's sources, extraction methods, chemical modifications, bioactivities, and its wide-ranging applications in drug delivery and tissue engineering.
**Methods:** The authors conducted a narrative review of recent literature, summarizing findings on chitosan extraction from marine (crustaceans, mollusks), terrestrial (insects), and microbial (fungi) sources. They detail chemical and biological extraction techniques, including demineralization, deproteinization, and deacetylation processes. The review covers various chitosan derivatives (e.g., N-carboxymethyl chitosan, thiolated chitosan, quaternary chitosan) and their preparation methods. Applications are discussed based on published studies, including in vitro and in vivo experiments, with specific examples of drug delivery systems (nanoparticles, hydrogels, films, microspheres) and tissue engineering scaffolds.
**Key Results:** The review highlights that chitosan exhibits broad-spectrum antibacterial activity against both gram-negative and gram-positive bacteria, with mechanisms involving cell wall disruption and leakage of cellular components. Antifungal activity against Candida albicans and other fungi is noted, with efficacy dependent on molecular weight and degree of deacetylation. Antiviral and anti-tumor activities are also reported, with chitosan derivatives showing potential as HIV-1 fusion inhibitors and anticancer agents. In drug delivery, chitosan-based systems have been developed for oral (e.g., cinnamyl-chitosan tablets with enhanced mechanical strength), ophthalmic (e.g., cholesterol-chitosan particles for dexamethasone delivery with sustained anti-inflammatory activity), transdermal (e.g., oxidized chitosan-modified nanofibers for sustained acyclovir release), nasal (e.g., thermosensitive hydrogels for nose-to-brain ibuprofen delivery), and vaginal (e.g., chitosan-alginate microspheres for cefixime with mucoadhesion >2 h) routes. In tissue engineering, chitosan scaffolds have demonstrated bone regeneration (e.g., biphasic calcium phosphate/chitosan membranes achieving ~57% new bone formation in rat calvarial defects), cartilage regeneration (e.g., multi-layered chitosan scaffolds with controlled porosity supporting mesenchymal stem cell differentiation), cardiac tissue regeneration (e.g., chitosan/dextran/β-glycerophosphate hydrogels upregulating cardiac markers cTnI and Cx43), corneal regeneration (e.g., chitosan-polyethylene glycol films with >95% transparency), periodontal regeneration (e.g., tri-layer chitosan membranes inducing 62.03% new bone formation in beagle dogs), and wound healing (e.g., micro-channeled alkylated chitosan sponges achieving hemostasis in <4 s and outperforming commercial agents in rat liver perforation models).
**Clinical Implications:** Chitosan's versatility and biocompatibility make it a valuable material for developing advanced drug delivery systems and tissue engineering scaffolds. Its mucoadhesive properties enhance drug retention at mucosal sites, improving bioavailability and patient compliance. The antimicrobial and hemostatic properties of chitosan-based dressings can accelerate wound healing and reduce infection risk. In tissue regeneration, chitosan scaffolds can support cell growth and differentiation, offering potential treatments for bone defects, cartilage injuries, corneal damage, and periodontal disease. However, challenges such as stability, reproducibility, and the need for further clinical translation remain. Future research should focus on optimizing chitosan modifications and combination with other materials to address these limitations and fully realize its clinical potential.