Enzyme‐Responsive Composite Hydrogel Coating Containing Nano‐HA/Nano‐ZnO with Pro‐Osteogenic and Anti‐Osteoclastic Properties

Abstract

The treatment of osteoporotic bone defects remains challenging due to the pathological microenvironment with impaired regenerative capacity and imbalanced bone formation and resorption. In this study, a methacrylated gelatin (GelMA) and methacrylated chitosan (CSMA) composite hydrogel coating is developed on poly(phthalazinone ether nitrile ketone) (PPENK), showing pro‐osteogenic and anti‐osteoclastic effects in vitro. Nano‐zinc oxide (nano‐ZnO), nano‐hydroxyapatite (nano‐HA), and phosphate‐ester‐functionalized alendronate (ALNP) are incorporated to confer antibacterial activity, promote osteogenesis, and enable enzyme‐responsive release of anti‐osteoporosis alendronate (ALN). SEM/EDS results confirm the homogeneous dispersion of the nanoparticles within the porous hydrogel. The stability of the hydrogel coating is verified by smooth scratch edges and no visible detachment in the cross‐hatch test. ALN release experiments confirm that the release amount of ALN is positively correlated with alkaline phosphatase (ALP) concentration, indicating significant enzyme‐responsive characteristics. In vitro studies show that the hydrogel coating on PPENK exhibits antibacterial activity. Nano‐HA and nano‐ZnO enhance the expression of osteogenic‐related genes and proteins in MC3T3‐E1 pre‐osteoblasts. The released ALN inhibits the receptor activator of nuclear factor‐κB ligand (RANKL)‐induced differentiation of RAW264.7 macrophages into osteoclasts. Overall, this surface modification strategy integrates enzyme‐responsive ALN release with composite hydrogel coating on PPENK, realizing antibacterial, osteogenic, and anti‐osteoclastic effects in vitro.