From molecular design to clinical translation: A critical and integrated review of chitosan structure–property performance relationships

Chitosan is a structurally versatile and functionally adaptable biopolymer that has attracted significant attention across pharmaceutical, biomedical, environmental, and food-related applications due to its biocompatibility, biodegradability, and intrinsic cationic nature. Despite extensive research, the field remains hindered by fragmentation of knowledge, inconsistency in material characterization, and limited integration of quantitative structure–property–function relationships necessary for predictive material design. This review addresses these challenges by adopting a structured and reproducible methodological framework to systematically evaluate chitosan research published between 2020 and 2025, drawing from major scientific databases and emphasizing studies that report well-defined molecular parameters alongside measurable functional outcomes. At the molecular level, the functional performance of chitosan is governed by key parameters such as degree of deacetylation, molecular weight, and substitution patterns, which collectively influence solubility, charge density, viscosity, crystallinity, and reactivity. This work critically examines how these intrinsic characteristics dictate physicochemical behaviour and necessitate targeted chemical or physical modifications to achieve application-specific performance. The review further provides a detailed analysis of industrial production pathways, comparing conventional chemical processing—characterized by high efficiency and scalability but associated with molecular degradation and environmental burden. This is alongside emerging biological and hybrid methods that offer improved molecular weight preservation, reduced toxicity, and enhanced sustainability, albeit with limitations in cost and scalability. In addition, the role of advanced physicochemical characterization techniques is highlighted as central to linking molecular structure with functional performance. Techniques such as Fourier transform infrared spectroscopy, nuclear magnetic resonance, gel permeation chromatography, zeta potential analysis, and dynamic light scattering enable precise determination of chemical composition, molecular weight distribution, surface charge, and particle behaviour. However, the absence of standardized protocols and inconsistent reporting across studies significantly limits reproducibility, comparability, and the development of robust predictive models. Critical research gaps are identified, including the lack of multivariate and non-linear analytical approaches, insufficient in vivo validation of chitosan systems, discrepancies between laboratory and clinical performance, and challenges in achieving controlled degradation and sustained functionality under physiological conditions. Furthermore, issues related to scalability, environmental sustainability, and regulatory standardization continue to impede industrial translation. Future research directions therefore emphasize the integration of systematic experimental datasets with computational modelling and machine learning approaches to establish predictive design frameworks, alongside the development of harmonized characterization standards, green manufacturing strategies, and comprehensive long-term biological evaluations. Overall, this review advances a transition from empirical and descriptive research toward a quantitative, reproducible, and mechanistically informed understanding of chitosan systems. By bridging molecular design, processing strategies, characterization techniques, and application performance, it provides a coherent foundation for the rational development and clinical translation of next-generation chitosan-based materials.