Accelerated Bone Regeneration by an Astaxanthin-Modified Antioxidant Aerogel through Relieving Oxidative Stress via the NRF2 Signaling Pathway

Bone regeneration of critical-sized bone defects (CSBDs) with biomimetic collagen-based aerogels remains a significant challenge due to the oxidative stress on the microenvironment. The excessive oxidative stress could induce apoptosis and dysfunction of host-derived cells. Astaxanthin (ATX) exhibits excellent antioxidant ability to block free radical chain reactions. In the present study, hybrid antioxidant collagen-derived aerogels (ATX–Col aerogels) were fabricated by a simple one-step method through the covalent cross-linking of Col and ATX. The resulting ATX–Col aerogels show porous and interconnected structures due to freeze-drying strategies. The ATX–Col aerogels exhibited excellent biocompatibility and biosafety. Furthermore, ATX–Col aerogels demonstrated favorable antioxidant capacity by eliminating intracellular ROS by activating the NRF2 signaling pathway. Finally, excellent reparative effects in repairing rat cranial defects were observed in ATX–Col aerogels. Taken together, ATX–Col aerogels can accelerate bone regeneration by relieving oxidative stress via the NRF2 signaling pathway and act as a potential bone graft for CSBD. This study provides a simple method of developing antioxidant aerogels for bone regeneration