An Additive‐Fabricated Biphasic Scaffold for Procedurally Promoting Bone Regeneration via Antioxidant and Osteogenesis

The repair process of bone tissue includes the early inflammatory response period and the late tissue repair period. It has been widely approved to be beneficial to the repair of bone injury by procedurally inhibiting the inflammatory response in the early stage and promoting bone regeneration in the late stage. In this study, the nano-hydroxyapatite/Poly(glycolide-co-caprolactone) (n-HA/PGCL) scaffold loaded with icariin was fabricated by fused deposition modeling technique, and the quercetin-loaded GelMA was further filled into the scaffold pores via light-curing methods to form a biphasic scaffold loaded with dual molecules (PHI + GQ scaffold). The releases of icariin and quercetin were sequential due to different degradation rates of GelMA and PGCL. In vitro, the scaffold not only scavenged reactive oxygen species production, but also promoted osteogenic differentiation of the MC-3T3-E1 cells. Furthermore, in vivo bone reconstruction of PHI + GQ scaffold was better than other groups by assessment of micro-CT data. In addition, the immunofluorescence staining of Arg-1 and iNOS indicated that PHI + GQ scaffold created an immune microenvironment conducive to bone repair due to the release of quercetin in the early stage, and HE and Masson staining suggested that PHI + GQ scaffold induced more new bone formation. These results demonstrated that the biphasic scaffold loaded with icariin and quercetin had both antioxidants in the early stage and osteogenesis properties in the late stage, obtaining satisfactory bone repair outcomes. Thus, the biphasic scaffold loaded with icariin and quercetin for sequential release could provide a promising solution for the restoration of bone defects and represent a potential strategy for bone regeneration.