Dual‐Crosslinking of Hyaluronic Acid–Calcium Phosphate Nanocomposite Hydrogels for Enhanced Mechanical Properties and Biological Performance

Herein, a facile approach for synthesizing mechanically enhanced nanocomposite hydrogels via a dual‐crosslinking process is described. Additional ionic crosslinking using various cations is introduced after an in situ precipitation process for hydroxyapatite immobilization in hyaluronic acid hydrogels (HAc–CaP). Ca2+, Ba2+, and Sr2+ ions exhibit the highest efficiencies in reinforcing the mechanical properties of HAc–CaP hydrogels. In addition, the dual‐crosslinked HAc–CaP hydrogels promote the biological responses of preosteoblast cells, which exhibit highly stretched shapes and greatly enhanced proliferation. Furthermore, the nanocomposite hydrogels achieve enhanced bioactivity by supporting osteogenic differentiation. Thus, enhancement on both the mechanical and biological properties of hyaluronic‐acid‐based nanocomposite hydrogels is achieved through this dual‐crosslinking process, e…