Nanozyme Hydrogel Promotes Bone Regeneration Via Cilia Regulation

Bone tissue damage and defects are common medical issues in both dentistry and general medicine. Globally, approximately 2.2 million bone graft surgeries are performed annually, highlighting the urgent clinical need for efficient and safe bone repair and regeneration materials. During bone repair, cells perceive the extracellular matrix microenvironment through cilia, and the absence of cilia significantly impairs this process. However, whether regulating cilia to enhance cellular sensing can promote bone regeneration remains unclear. This study aims to construct a multifunctional antioxidant hydrogel platform to modulate cilia occurrence. We constructed a multifunctional biomimetic extracellular matrix (ECM) platform using hydrogel materials. Leveraging mineralization-promoting short peptides screened by our team via AI deep learning, we employed chemical modification to graft hydrophobic heads, thereby altering their hydrophilic properties and enhancing compatibility with water-insoluble drugs. This enabled the development of a pH-responsive supramolecular hydrogel. To further improve mechanical strength, chondroitin sulfate grafted with double bonds was utilized as a crosslinker alongside small-molecule monomers. Under UV initiation, nanozymes facilitated gelation, forming a dual-network structure integrating supramolecular and polymeric frameworks. This study developed a cilia-regulating hydrogel system via nanozyme-photoinitiated fabrication. The hydrogel exhibits excellent antioxidant properties, enhances cilia occurrence, and promotes osteogenesis both in vitro and in vivo. This study elucidates the hydrogel’s unique gelation mechanism and explores its biological utility, demonstrating cilia-mediated enhancement of bone regeneration.