Injectable nanostructured strontium-doped calcium phosphate scaffolds as a chemioterapic drug delivery for osteosarcoma treatments

Introduction Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. Osteosarcoma (OS) cancer treatments include systemic chemotherapy and surgical resection. Novel therapeutic techniques, which use drug-delivery system to reduce side effects and increase treatment efficacy, have been presented in recent years. Anticancer drugs delivered locally exhibit enhanced tumor-killing efficacy, decreased drug resistance, and limited systemic effects compared to high local concentrations Experimental methods Herein, injectable nanostructured strontium-doped calcium phosphate scaffold (SrCPC) was investigated as drug delivery system to combine bone regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC-MTX and SrCPC-DOX, respectively. The cytocompatibility of SrCPC was investigated using SEM analysis, Alamar Blue metabolic test, Live/dead staining, immunohistochemistry for cellular cytoskeleton organization and Real-Time PCR Array to test gene expression of ECM molecules in human adipose stem cells (hASC). SrCPC osteogenic markers like mineral matrix deposition, osteocalcin protein (OCN) and differentially expressed genes (DEG) involved in the skeletal development pathway were also performed. The SrCPC-MTX and SrCPC-DOX, were tested in an in vitro model of human OS cell lines SAOS-2, engineered OS cell line (SAOS‐2‐eGFP) and U2-OS. The ability of scaffolds to induce OS cell death was assessed evaluating cell proliferation and apoptosis markers. To determine if OS cell lines grown on doped‐scaffolds change their migratory ability and invasiveness, a wound‐healing assay was performed