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.