Natural Product Based Hydrogels in Biomedicine: Design Strategies and Crosslinking Mechanisms

Hydrogels have found extensive applications in the medical field owing to their designability, biocompatibility, and self-supporting characteristics. Natural products, possessing multiple pharmacological activities and relatively low toxicity compared to chemical drugs, exhibit unique advantages in the field of hydrogel-related therapy. This review examines three major design strategies for natural product-based hydrogels from the perspective of how natural products interact with hydrogel networks: self-assembly of natural small molecules, physical encapsulation of natural products, and chemical conjugation of natural products to polymer matrices. These strategies determine the forms in which natural products are incorporated into hydrogels. Natural products may be encapsulated as bioactive components, participate in gelation behavior as matrices or crosslinking agents, or form nanoparticles embedded within the hydrogels. This review further analyzes the effects of these design strategies on hydrogel mechanical properties, retention of biological activity and drug-release behavior, and summarizes their application characteristics in biomedical fields. Finally, the advantages, limitations, and development prospects of the different design strategies are discussed. This review aims to provide guidance for the rational design, synthesis, and application of natural product hydrogels according to the properties of natural products and specific biomedical requirements.