Development of a multi-functional naringin-loaded bioglass/carboxymethyl chitosan/silk fibroin porous scaffold for hemostasis and critical size bone regeneration.

Persistent bleeding and limited repair capacity greatly threaten patients with bone destruction. Designing inorganic-organic biomimetic scaffolds with quick hemostasis and osteogenesis functions will solve this problem. A novel degradable and naringin (NG) loaded porous scaffold (SCB-N) based on APTES-modified bioactive glass (ABG), carboxymethyl chitosan and silk fibroin is developed. ABG and NG enhance the strength of the scaffolds. The scaffolds can release NG and bioactive ions (Ca and Si), promoting the expression of osteogenesis (OCN, BMP-2), angiogenesis (VEGF), and neurogenesis (TB3, GFAP) genes in bone mesenchymal stem cells (BMSCs) and the related proteins (OCN, BMP-2, VEGF, GFAP). When implanting the scaffolds in rat cranial critical size defects, all scaffolds exhibit good compatibility, and SCB-N2 (with ABG and 1 mg/mL NG) group significantly promotes new bone regeneration and the formation of M2-type macrophages. Transcriptome sequencing results confirmed the osteogenic differentiation of BMSCs stimulated by SCB-N2 scaffolds is mainly regulated through MAPK and Wnt signaling pathways. Moreover, SCB-N2 group demonstrates quick hemostasis in vitro and in vivo due to the high adsorption ability and Ca ions release. The novel bionic scaffolds loaded with ion/traditional Chinese medicine monomer, possess the capabilities of hemostasis, neurovascularization, osteogenesis and immunomodulation, therefore exhibiting potential in bone repair.