Oxygen‐Carrying and Antibacterial Fluorinated Nano‐Hydroxyapatite Incorporated Hydrogels for Enhanced Bone Regeneration

Abstract Insufficient oxygen availability in tissue engineering is one of the major factors for the failure of clinical transplantation. One potential strategy to conquer this limitation is the fabrication of spontaneous and continuous oxygen supplying scaffolds for in situ tissue regeneration. In this work, a versatile fluorine‐incorporating hydrogel is designed which can not only timely and continuously supply oxygen for mesenchymal stem cells (MSCs) to overcome deficient oxygen before vascularization in scaffolds, but can present a higher antibacterial capability to avoid bacterial infections. The HAp@PDA‐F nanoparticles are first prepared and then incorporated with the quaternized and methacrylated chitosan forming CS/HAp@PDA‐F by photo‐crosslinking. In vitro results indicate that CS/HAp@PDA‐F hydrogel has outstanding mechanical performance, moreover, it also has the oxygen‐carrying ability to prolong survival ability, enhance proliferation activity, and preserve osteogenic differentiation potency and promote osteogenic‐related genes expression of rat bone mesenchymal stem cells (rBMSCs) under hypoxic environment. Furthermore, the CS/HAp@PDA‐F hydrogel can inhibit the growth of Staphylococcus aureus and Escherichia coli , providing a good antibacterial activity. Additionally, in vivo experiments demonstrate higher bone volume and bone mineral density, and more new bone tissue generation in CS/HAp@PDA‐F group than in CS/HAp@PDA group. These results indicate that the rational design of fluorinated hydrogel possesses a good clinical application prospect for bone regeneration.