Injectable, pro-osteogenic and antioxidant composite microspheres composed of cerium-containing mesoporous bioactive glass and chitosan for bone regeneration applications

Repair of bone defects caused by excess reactive oxygen species (ROS) remains a clinical challenge. It is essential to inhibit the overaccumulation of ROS to accelerate the bone healing process. Herein, we developed an injectable composite phenylboronic acid-modified chitosan microspheres (CSP@BG) containing cerium-doped mesoporous bioactive glass nanoparticles (Ce-MBGNs) using a W/O emulsification method and investigated the structure, antioxidant, and osteogenic activity of microspheres. We systematically evaluated the microscopic morphology and chemical structure of the microspheres using FT-IR, XRD, SEM and TGA. When the content of incorporated Ce-MBGNs ranged from 0.83 to 14.37 wt%, the microspheres retained their morphology and their particle size varied from ∼10 to ∼23 μm. In vitro tests indicated that the CSP@BG microspheres exhibited desirable antioxidant activity, scavenged a variety of ROS such as H2O2 and ·OH, and demonstrated significant DPPH radical scavenging efficiency with up to 72.8% DPPH was scavenged. In addition, the results of CCK8 assay, ALP and ARS staining, and RT-PCR assay demonstrated that the CSP@BG microspheres could significantly promote the proliferation and osteogenic differentiation of human bone marrow stromal cells by tuning the amount of Ce-MBGNs added. In conclusion, this study systematically investigated the effects of Ce-MBGNs content on the morphological characteristic, antioxidant properties, and osteogenic activity of CSP@BG microspheres. Our results demonstrate the potential of pro-osteogenic and antioxidant composite microspheres composed of Ce-MBGNs and chitosan for bone regeneration applications.