Development of a borosilicate bioactive glass scaffold incorporating calcitonin gene-related peptide for tissue engineering.

Abstract

Protein delivery and release from synthetic scaffold materials are major challenges within the field of bone tissue engineering. In this study, 13-93B1.5 borosilicate bioactive glass (BSG) base paste was 3D printed to produce BSG-based scaffolds with high porosity (59.85±6.04%) and large pore sizes (350-400μm) for functionalization with a sodium alginate (SA)/calcitonin gene-related peptide (CGRP) hydrogel mixture. SA/CGRP hydrogel was uniformly filled into the interconnected pores of 3D printed BSG constructs to produce BSG-SA/CGRP scaffolds which were subject to bioactivity and biocompatibility analysis. BSG scaffolds filled with SA hydrogel underwent dissolution in simulated body fluid (SBF), resulting in the precipitation of hydroxyapatite (HA) on the borosilicate glass evidenced by scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Around 90% of CGRP was released from scaffolds after 7days of immersion in SBF, reaching a final released concentration of 893.00±63.30ng/mL. Cellular adhesion, proliferation, and differentiation of human bone marrow mesenchymal stem cells (HBMSCs) cultured with BSG-SA/CGRP scaffolds revealed improved biocompatibility and osteogenic capabilities compared with BSG-SA scaffolds in the absence of CGRP. When subcutaneously implanted in rat models, BSG-SA/CGRP scaffolds induced low localized inflammation without causing bodily harm in vivo. Findings revealed that bioactive glass scaffolds incorporating CGRP met the scaffold requirements for bone regeneration and that the addition of CGRP promoted osteogenic differentiation where it may potentially be utilized for future regenerative applications.