Polyurethane–Chitosan Composites for Tissue Engineering: Novel Strategies, Therapeutic Potential and Limitations

Polyurethane–chitosan (PU–CS) composites have emerged as promising biomaterials for tissue engineering because they combine the tunable mechanical properties, elasticity, processability, and degradation behavior of polyurethanes (PU) with the hydrophilicity, biological functionality, and antimicrobial properties of chitosan (CS). This review critically analyzes PU–CS composites with particular emphasis on the relationships between polymer composition, intermolecular interactions, phase organization, scaffold architecture, physicochemical properties, degradation, and biological performance. Particular attention is given to hydrogen bonding and other interfacial interactions governing composite organization, as well as to the effects of PU chemistry, CS molecular characteristics, PU/CS ratio, porosity, fiber organization, and fabrication strategy. Cross-study comparison indicates that no single PU/CS composition or scaffold architecture is universally optimal and that regenerative performance cannot be predicted from polymer ratio alone. Instead, composition must be considered together with hydration, mechanics, morphology, biodegradation kinetics, and tissue-specific requirements. Current evidence demonstrates promising cytocompatibility and regenerative potential of PU–CS systems, particularly in wound healing and selected bone, cardiovascular, and other tissue-engineering applications. However, the evidence base remains predominantly preclinical. Major barriers to translation include raw-material variability, insufficient standardization, limited long-term and large-animal data, manufacturing reproducibility, sterilization effects, scale-up, and regulatory complexity. Emerging approaches, including advanced biofabrication, computational modeling, and artificial intelligence, may further support PU–CS development, although their direct application to this material class remains limited. Overall, future progress will depend on shifting from descriptive optimization of individual scaffold properties toward reproducible, quantitatively characterized, and translationally oriented PU–CS biomaterial design. This review critically evaluates recent progress in PU–CS composite biomaterials by integrating evidence from fundamental polymer chemistry, materials engineering, biology, regenerative medicine, and translational biomaterials research.