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 2+ and Si 4+ ), 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.