Functionalization Strategies of Non-Isocyanate Polyurethanes (NIPUs): A Systematic Review of Mechanical and Biological Advances

Conventional polyurethane (PU) synthesis is associated with environmental and health concerns due to the use of toxic isocyanates. In recent years, the development of non-isocyanate polyurethanes (NIPUs) has emerged as a sustainable alternative to conventional polyurethanes. However, these materials still exhibit inconsistencies in their physicomechanical and biological properties. This systematic review was conducted following the PRISMA methodology. A total of sixteen studies published between 2015 and 2025 were analyzed, focusing on functionalization techniques developed for non-isocyanate polyurethanes to evaluate their influence on physicomechanical and biological performance. The results reveal that functionalization can be achieved through the incorporation of inorganic additives, polar or ionic groups, and polymeric modifiers. Among the analyzed systems, those functionalized with azetidinium and Polyethylene glycol diacrylate (PEGDA) exhibited the most balanced performance, combining high mechanical strength, low cytotoxicity, and effective antibacterial activity. Overall, these functionalizations have demonstrated significant improvements in tensile strength, thermal stability, hydrophilicity, and antimicrobial activity, facilitating broader industrial and biomedical applications. Consequently, this review concludes that functionalization plays a pivotal role in improving the overall performance of non-isocyanate polyurethanes. It represents an effective and sustainable strategy to enhance the physicomechanical and biological behavior of these materials, supporting their development for advanced applications such as bioactive coatings, membranes, and wound dressings.