Fabrication of Micro-Nano Bioactive Glass Scaffold Incorporated with Siglec-15 for Bone Repair and Postoperative Treatment of Osteosarcoma

Abstract

This study aimed to fabricate micro-nano bioactive glass (MNBG) scaffolds loaded with chemotherapeutics and siglec-15 monoclonal antibody with bone repair capability and high-active drug loading capability for postoperative treatment of osteosarcoma. Bioactive glass (BG) particles were incorporated with siglec-15 mAb and gemcitabine through mesopores and calcium ions on the surface. Dendritic cells (DCs) were treated with siglec-loaded BGs and gemcitabine. RT-qPCR analysis was conducted to detect DJ-1 and PTEN mRNA levels, CCK-8 technology to detect cell activity, and flow cytometry to detect cell apoptosis. Rats were administrated with siglec-15-MNBG composite scaffolds with/without gemcitabine. 3D printing was used to determine adhesion strength of each group. Administration of MNBG scaffold decreased the expression of PTEN and up-regulated expression of DJ-1 when inducing cell apoptosis. Combined treatment with gemcitabine augmented adhesion of material and enhanced phosphorylation activity of p-AKT, mitigating the inhibitory effect of scaffold loaded with siglec-15 on p-AKT protein expression. Collectively, MNBG scaffold loaded with siglec-15 might promote bone regeneration and incorporate with chemotherapeutic drugs to suppress tumor development and promote apoptosis through PTEN/PI3 K pathway. These findings provide a novel insight into postoperative treatment of osteosarcoma and help development of tumor immunotherapy/bone repair integrated materials.