Micelle-Facilitated Gelation Kinetics and Viscoelasticity of Dynamic Hyaluronan Hydrogels for Bioprinting of Mimetic Constructs and Tissue Repair

Engineered tissues created through cell-laden hydrogel bioprinting offer a promising therapeutic approach for tissue regeneration. However, considerable challenges persist in the development of hydrogels that possess optimal gelling kinetics and viscoelastic properties, and sufficient stability to facilitate both the printing of biomimetic structures and the formation of engineered tissues. Herein, we present a rapidly gelling and long-term dynamic hyaluronate hydrogel achieved through the introduction of self-assembled F127 diacrylate (F127DA) micelles to modulate the kinetics of hydrazone crosslinking and the extent of dual-crosslinking network formation. The investigation demonstrates that the introduction of F127DA strengthens the interactions among the hyaluronate components, significantly accelerating gelation and increasing the mechanical stability of the optimal hydrogels. The rapidly formed ink permits low-shear mixing-injection printing, facilitating the construction of precise structures with high cell viability. The viscoelastic microenvironment fosters fibroblast spreading within the bioprinted matrices and supports the development of a biomimetic skin construct characterized by multilayer keratinocytes on the surface. Application of this dynamic hydrogel in a full-thickness mouse skin wound model accelerates tissue healing by inflammation suppression, angiogenesis and extracellular matrix promotion. This study demonstrates innovative modulation of gelation kinetics and viscoelasticity of dynamic hyaluronic hydrogels using block copolymer micelles for tissue engineering.