DOI: 10.3390/pharmaceutics18070820 ISSN: 1999-4923

Natural Polymer-Based Hemostatic Hydrogels with Advanced Material and Structural Designs for Functional Applications

Lixin A, Zhaoming Guo, Chen Zhao, Guangyao Li, Xinwen Xu, Yongai Yu, Peng Qu, Qiang Liu

Uncontrolled hemorrhage remains a major challenge in trauma care and surgical interventions, where rapid hemostasis and wound sealing are essential for improving patient survival. Natural polymer-based hydrogels have emerged as promising hemostatic materials owing to their excellent biocompatibility, biodegradability, and biomimetic properties. However, their clinical translation remains limited by insufficient mechanical robustness, wet adhesion, and functional responsiveness. To address these challenges, considerable progress has been achieved through rational material design and structural engineering strategies. Representative natural polymers, particularly polysaccharides and proteins, exhibit distinct physicochemical and biological characteristics that determine their hemostatic mechanisms and design strategies. Based on these material platforms, molecular modification strategies, including charge regulation, hydrophobic modification, and bioactive functionalization, have been widely employed to modulate interfacial interactions, platelet adhesion, coagulation activation, and tissue adhesion. In parallel, advanced structural architectures, such as porous, particulate, fibrous, multicrosslinked/multinetwork, and nanocomposite systems, have significantly enhanced fluid absorption, mechanical resilience, stress dissipation, and hemorrhage sealing efficiency. Beyond conventional hemostasis, increasing efforts have focused on integrating multifunctional properties, including antibacterial activity, inflammatory regulation, oxidative stress modulation, tissue regeneration, dynamic monitoring, and stimuli-responsive behaviors. This review systematically summarizes recent advances in natural polymer-based hemostatic hydrogels from the perspectives of advanced material modification strategies, structural engineering approaches, and functional integration, with particular emphasis on the relationships among material characteristics, interfacial behavior, structural organization, and hemostatic performance. Finally, current challenges and future perspectives for clinical translation are discussed, aiming to provide valuable insights for the rational design and clinical implementation of next-generation hemostatic biomaterials.

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