Serum‐Integrated Dopamine–Hyaluronic Acid Hydrogels for Injectable Soft‐Tissue Microenvironment Modulation
Hyaluronic acid (HA) hydrogels are widely used as injectable fillers for soft‐tissue augmentation; however, most currently available formulations primarily provide structural support with limited biological activity. This work establishes design principles for integrating autologous biological components into catechol‐based HA (DaHA) hydrogels and underscores the potential of DaHA–serum systems as bioactive injectable platforms. In this study, human whole serum was incorporated into DaHA hydrogels bsy replacing the aqueous phase during hydrogel preparation (0%–10% v/v). Serum incorporation accelerated gelation and altered the viscoelastic behavior of the resulting hydrogels while maintaining injectability through small‐gauge needles. Rheological characterization demonstrated stable gel formation, shear recovery, and favorable mechanical properties, whereas moderate serum incorporation (under 10% v/v) preserved swelling behavior and structural stability. Sustained release of serum‐derived proteins was observed for at least 8 days, indicating prolonged biochemical availability within the hydrogel matrix. In vitro studies using L929 fibroblasts demonstrated suitable cytocompatibility and enhanced cell survival under serum‐free culture conditions. Subcutaneous implantation further confirmed good in vivo tolerance, minimal inflammatory response, and gradual tissue integration. These findings demonstrate that controlled incorporation of human serum provides a practical strategy for engineering bioactive catechol‐based hydrogels while preserving the physicochemical properties required for injectable soft‐tissue filler applications.