Tyramine-modified hydrogels for tissue engineering: characterizations, crosslinking methods, and applications-a...

Hydrogels, as three-dimensional (3D) hydrophilic polymer networks, have gained widespread attention in tissue engineering (TE) due to their high-water content, porosity, biocompatibility, and structural similarity to the native extracellular matrix. Injectable andin situforming hydrogels offer additional advantages by enabling minimally invasive delivery directly to injury sites, reducing patient discomfort, and improving clinical accessibility. Among these, tyramine (Tyr)-modified hydrogels have emerged as a promising class of biomaterials, combining enhanced biocompatibility, bioactivity, and mechanical properties through the incorporation of phenolic groups. This functionalization enables enzymatic and light-mediated cross-linking under mild physiological conditions, providing precise control over hydrogel stiffness, degradation, and cell-interacting properties. This review comprehensively covers recent advances in the synthesis, modification, and cross-linking strategies of Tyr-conjugated polymers, particularly enzymatic methods mediated by horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂), as well as light-mediated methods, and their impact on the properties of hydrogels. It also further explores the broad applications of Tyr-modified hydrogels in TE, including bone and cartilage regeneration, wound healing, vascular and cardiac repair, and 3D bioprinting. Finally, it discusses current challenges and future perspectives for Tyr-modified hydrogels in regenerative medicine.