Chitosan in regenerative medicine: a translational perspective on biomaterial design

Abstract

Chitosan is an aminopolysaccharide platform with broad relevance to regenerative medicine because its charge density, solubility, degradation, processability, and biological interactions can be adjusted through source selection, deacetylation chemistry, molecular-weight control, derivatization, and formulation. However, this tunability is accompanied by substantial source- and process-dependent variability, which represents a central translational challenge: materials labelled as chitosan can differ markedly in degree of deacetylation, molecular weight, pattern of acetylation, polydispersity, purity, endotoxin and β-glucan burden, residual reagents, sterilization history, and final architecture. This review synthesizes chitosan regenerative biomaterials from a translational design perspective. We examine raw-material provenance, crustacean and fungal sources, extraction and deacetylation routes, physicochemical determinants, medical-grade purity requirements, host-biointerface mechanisms, antimicrobial activity, scaffolds, hydrogels, coatings, bioinks, polymer composites, and functionalization with growth factors, drugs, peptides, and extracellular vesicles. We also address ethical, cell-related, regulatory, and manufacturing issues that arise when chitosan is combined with animal-derived inputs, antibiotics, growth factors, living cells, or extracellular-vesicle preparations. Across applications, the evidence indicates that chitosan should not be treated as a universally biocompatible, universally antimicrobial, or intrinsically regenerative polymer. Rather, it is a tunable, formulation-dependent biomaterial platform whose performance depends on defined chemical attributes, exposure route, biological context, and clinically relevant comparators. Translation will require standardized reporting of degree of deacetylation, molecular weight, acetylation pattern, purity, endotoxin and β-glucan controls, sterilization effects, degradation, release kinetics, post-release bioactivity, and product-specific biological evaluation. Regulatory-aware design, reproducible manufacturing, and mechanism-linked potency assays are essential for moving chitosan-based regenerative systems from promising preclinical constructs toward credible clinical products.