Imaging Oxygen Concentrations in Bone Scaffolds during Cellular Activity and Fluid Perfusion

Abstract

Developing bone replacement scaffolds has been a driving ambition of regenerative medicine. Although great progress has been achieved for small scaffolds, the real clinical need is for large scaffolds >5 mm. Oxygenating these scaffolds is challenging, as slow diffusion rates lead to necrotic regions in the scaffold core. In this work, we modulate in vitro oxygen concentration in a scaffold in a flow chamber using an external perfusion pump while imaging oxygen concentrations below the scaffolds. With no external flow, yeast cells growing in the scaffold deplete oxygen, especially from the center, with concentrations reaching a steady state consistent with reaction-diffusion models. The oxygen is restored via pumping fresh medium through the scaffold. The oxygen profiles are highly reproducible from cycle to cycle. This lays the groundwork for future in vivo oxygen imaging studies using localized light sources and external perfusion pumps for modulation.