Cobalt‐Doped Monetite‐Induced Biomimetic Hypoxia Camouflages Osteogenic Healing Microenvironment

Abstract

To address developing novel biomimetic material able to camouflage osteogenic healing microenvironment, this study looked to synthesize and characterize a cobalt-doped monetite (CoCaP). After synthesizing, the samples were subjected to physicochemical and biological characterization a comprehensive structural analysis encompassing a suite of complementary techniques. Previously, our data show a validation and reveal distinct structural alterations from cobalt doping. Biologically, Co-doped monetite had no cytotoxic effects on osteoblasts up to 7 days; rather, it contributed to osteoblast adhesion and migration, here estimated by carrying out a wound healing assay. Thereafter, we have linked this phenomenon to an upregulation of cyclin-dependent kinases (CDKs) genes, and it was hypothesized to be related to the dynamic adhesion-related machinery requiring the upregulation of integrins, focal adhesion kinase (FAK), and Src. Complementarily, osteoblast differentiation was also investigated, and our data clearly show a strong stimulus of osteogenic phenotype, once it was shown a significantly increased upregulation of both classical osteogenic transcription factors Runx2 and Osterix, both in response to Co-doped monetite. Additionally, we observed extracellular matrix (ECM) remodeling requiring the activities of matrix metalloproteinase 9 (MMP9) zymogens, suggesting effective collagen turnover along osteoblast differentiation and mineralization. Collectively, our findings show the biological impact of Co-doped monetite on the osteogenic phenotype of pre-osteoblasts. Notably, cobalt-doped monetite induces biomimetic hypoxia, and it recapitulates relevance on the osteogenic phenotype required for the bone healing microenvironment. Thus, Co-doped monetite emerges as a biomimetic and "smart" advanced material for promising applications in bone injuries or the bioactive surface of dental implants in the future.