Ultra‐Fine 3D Bioprinting of Dynamic Hyaluronic Acid Hydrogel for in Vitro Modeling

Abstract

Abstract3D bioprinting bridges tissue engineering and additive manufacturing, however developing bioinks with balanced biological and physical properties remains a challenge. Hyaluronic acid (HA) is a promising base material due to its biocompatibility and cell‐recognition features. An HA‐based bioink is designed using dynamic disulfide‐crosslinking at physiological pH by modifying HA with cysteine moieties. To overcome the slow gelation kinetics typical of disulfide‐crosslinked hydrogels, potassium iodide (KI) is introduced, accelerating gelation in a concentration‐dependent manner. KI not only enhances gelation but also provides radical scavenging properties while maintaining hydrogel integrity. A low KI concentration (50 mm) offers more than a 3 h printing window, ensures cell viability, and facilitates the use of fine needles (32G, 108 µm inner diameter). This enables the fabrication of large (>3 cm) and complex 3D structures. Using this bioink, an osteoarthritis disease model is developed to investigate interactions between human mesenchymal stromal cells (hMSCs) and chondrocytes, demonstrating the immunomodulatory effect of hMSCs on inflammation‐induced chondrocytes. Overall, the HA‐based bioink addresses critical challenges in 3D bioprinting, providing a robust platform for constructing innovative in vitro models and supporting advancements in disease modeling and precision medicine.