title: Feasibility of Spatially Offset Raman Spectroscopy for in Vitro and in Vivo Monitoring Mineralization of Bone Tissue Engineering Scaffolds.
abstract: 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 current instrument. The intensity ratio of Raman bands associated with the scaffolds and HA with the spatial offset depended on the depth at which HA was located. Furthermore, we show the feasibility for in vivo monitoring mineralization of scaffold implanted subcutaneously by demonstrating the ability to measure transcutaneously Raman signals of the scaffolds and HA (fresh chicken skin used as a top layer). The ability to measure spectral depth profiles at high speed (5 s acquisition time) and the ease of implementation make SORS a promising approach for noninvasive characterization of cell/tissue development in vitro, and for long-term in vivo monitoring the mineralization in 3D scaffolds subcutaneously implanted in small animals.
authors.affiliation: School of Physics and Astronomy, University of Nottingham , University Park, Nottingham NG7 2RD, United Kingdom.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Liao
authors.affiliation: School of Physics and Astronomy, University of Nottingham , University Park, Nottingham NG7 2RD, United Kingdom.
authors.forename: Faris
authors.initials: F
authors.lastname: Sinjab
authors.affiliation: Department of Materials, Imperial College London , SW7 2AZ, London, United Kingdom.
authors.forename: Amy
authors.initials: A
authors.lastname: Nommeots-Nomm
authors.affiliation: Department of Materials, Imperial College London , SW7 2AZ, London, United Kingdom.
authors.forename: Julian
authors.initials: J
authors.lastname: Jones
authors.affiliation: School of Pharmacy, University of Nottingham , University Park, Nottingham NG7 2RD, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Ruiz-Cantu
authors.affiliation: School of Pharmacy, University of Nottingham , University Park, Nottingham NG7 2RD, United Kingdom.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Pharmacy, University of Nottingham , University Park, Nottingham NG7 2RD, United Kingdom.
authors.forename: Felicity
authors.initials: F
authors.lastname: Rose
authors.affiliation: School of Physics and Astronomy, University of Nottingham , University Park, Nottingham NG7 2RD, United Kingdom.
authors.forename: Ioan
authors.identifier: 0000-0002-5360-230X
authors.initials: I
authors.lastname: Notingher
mesh_terms: D001672:Biocompatible Materials / Q000032:analysis; D001842:Bone and Bones / Q000737:chemistry*; D017886:Durapatite / Q000032:analysis*; D019344:Lactic Acid / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013059:Spectrum Analysis, Raman; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017886:Durapatite