Enzyme-mediated hydrogelation for biomedical applications: A review

Hydrogels possess significant potential for biomedical applications due to their flexibility and biocompatibility. However, current physical or chemical methods for their preparation often fail to balance biocompatibility and mechanical properties, limiting their application scope. Enzymatic preparation of hydrogels offers advantages including mild reaction conditions, absence of toxic substances, and superior biocompatibility. This review focuses on the enzymatic preparation systems of hydrogels and its application in the fast-growing biomedical field. Firstly, the mechanisms of enzyme-mediated hydrogel preparation can be categorized into four classes: enzyme cross-linking, enzyme polymerization, enzyme-mediated self-assembly of small molecular gelators, and enzyme-induced pH changes. Hydrogels prepared through the first two mechanisms retain the mechanical advantages of chemically cross-linked hydrogels while preserving the inherent biocompatibility. Additionally, hydrogels prepared via the latter two mechanisms exhibit rapid responses to external stimuli similar to physically crosslinked hydrogels while maintaining high biocompatibility. Furthermore, we discuss their application in biomedical scope and analyze the correlation between the mechanism of enzyme-mediated hydrogels and their respective application domains. Finally, the current challenges faced by enzymatically mediated hydrogelation are summarized; notably that enzymes incorporated and immobilized during hydrogel preparation remain active, resulting in catalytic activity exhibited by these enzymatically mediated hydrogels, which broadens their potential applications.