Feasibility of Spatially Offset Raman Spectroscopy for in Vitro and in Vivo Monitoring Mineralization of Bone Tissue Engineering Scaffolds.

We investigated the feasibility of using spatially offset Raman spectroscopy (SORS) for nondestructive characterization of bone tissue engineering scaffolds. The deep regions of these scaffolds, or scaffolds implanted subcutaneously in live animals, are typically difficult to measure by confocal Raman spectroscopy techniques because of the limited depth penetration of light caused by the high level of light scattering. Layered samples consisting of bioactive glass foams (IEIC16), three-dimensional (3D)-printed biodegradable poly(lactic-co-glycolic acid) scaffolds (PLGA), and hydroxyapatite powder (HA) were used to mimic nondestructive detection of biomineralization for intact real-size 3D tissue engineering constructs. SORS spectra were measured with a new SORS instrument using a digital micromirror device (DMD) to allow software selection of the spatial offsets. The results show that HA can be reliably detected at depths of 0–2.3 mm, which corresponds to the maximum accessible spatial offset of the curre...