Zinc doped amorphous calcium phosphate integrated GBR module role in facilitating bone augmentation via immunostimulation of osteogenesis

Abstract

Guided bone regeneration in the alveolar bone relies on the colonization and differentiation of immune cells within the defect area. The absence of osteoinductive and osteoimmune properties of currently available scaffolds hinders to achieve optimal repair outcomes in clinical settings. Thus, we aimed to enhance the bone repair ability of polycaprolactone (PCL) scaffolds by incorporating osteoinductive amorphous calcium phosphate (ACP) with immune-regulating zinc ions (ACP(Zn), ACZP), to create a favorable immunomodulatory microenvironment. After one day of co-culture with PCL-ACZP, the spreading area of macrophage cells can reach 47.6%, 2.7 times of that from the original PCL scaffold. Additionally, over 32.1% of macrophages exhibited M2 polarization was observed within three days of co-culture. The PCL-ACZP/macrophage-conditioned medium significantly boosted osteogenic gene expression in MC3T3-E1 cells. After eight weeks of implantation in a rat femoral condyle defect, the BV/TV from the PCL-ACZP group reached 32.9%, 1.4 times of that from the PCL group. Furthermore, the PCL-ACZP-GelMA biphasic module as prepared successfully achieved complete regeneration of three-walled alveolar bone defects in rabbits, resulting in arch-shaped alveolar bone repair and providing greater convenience in the clinical settings. This study showcased the effectiveness of PCL-ACZP-GelMA biphasic module as bioactive scaffolds in the morphological restoration of alveolar bone.