Intramembranous Ossification Imitation Scaffold with the Function of Macrophage Polarization for Promoting Critical Bone Defect Repair

The regeneration of craniofacial bone defects remains a crucial clinical challenge. To date, numerous biomaterials are applied in this field. However, current strategies have ignored the importance of intramembranous ossification and the vital role of macrophages in regulating osteogenesis. Here, an osteoblast (OB)-targeting peptide (SDSSD)-modified chitosan scaffold (CS-SDSSD) is developed for imitating the physiological process of bone development from the fibrous membrane. The addition of free peptide (fSDSSD) can recruit host OBs, and the peptide grafted on the scaffold (CS-SDSSD) can well organize the migrated OBs by binding with their surface periostin. Besides, macrophage polarization is found in the bone defects. CS-SDSSD + fSDSSD displays advantages in prioritizing M2 macrophage polarization and promoting the intramembranous ossification bone repair process. In summary, our strategy provides an economical and effective path for craniofacial bone repair and holds great potential for biomedical applications.