Raman Spectroscopic and Microscopic Analysis for Monitoring Renal Osteodystrophy Signatures

Abstract

Defining the pathogenesis of renal osteodystrophy (ROD) and its treatment efficacy are difficult, since many factors potentially affect bone quality. In this study, confocal Raman microscopy and parallel statistical analysis were used to identify differences in bone composition between healthy and ROD bone tissues through direct visualization of three main compositional parametric ratios, namely, calcium content, mineral-to-matrix, and carbonate-to-matrix. Besides the substantially lower values found in ROD specimens for these representative ratios, an obvious accumulation of phenylalanine is Raman spectroscopically observed for the first time in ROD samples and reported here. Thus, elevated phenylalanine could also be considered as an indicator of the disease. Since the image results are based on tens of thousands of spectra per sample, not only are the average ratios statistically significantly different for normal and ROD bone, but the method is clearly powerful in distinguishing between the two types of samples. Furthermore, the statistical outcomes demonstrate that only a relatively small number of spectra need to be recorded in order to classify the samples. This work thus opens the possibility of future development of in vivo Raman sensors for assessment of bone structure, remodeling, and mineralization, where different biomarkers are simultaneously detected with unprecedented accuracy.

Fabrication of Surfactant-Dispersed HiPco Single-Walled Carbon Nanotube-Based Alginate Hydrogel Composites as Cellular Products

“…HiPCO SWCNT (HR32-009) were obtained from NanoIntegris (Boisbriand, QC, Canada) and purified by a previously reported method [46]. Anhydrous calcium chloride (CaCl 2 ) was obtained from Sigma-Aldrich (St. Louis, MO, USA).…”

Multimodal characterization of the bone-implant interface using Raman spectroscopy and nanoindentation

“…Another indicator of bone remodeling is the carbonate-to-matrix ratio describing the evolution of carbonate minerals relative to amide I from the collagen matrix. Its significantly higher value in the newly formed bone tissue with a high standard deviation could also be explained by carbonate substitution and different remodeling stages [52].…”

“…Thus, the newly formed bone is composed of less mineral relative to matrix components, indicating lower mineralization and potential bone tissue maturation in process at the BII [33-35, 39, 54, 55]. Eventually, the mineral-to-matrix ν2PO4 3-/Amide III ratio, an indicator of calcium content [52], has lower values in newly formed bone tissue, as previously observed for bone maturation [56], bone healing [34], and osseointegration of a 3D printed titanium implant [39].…”

Assessment of Renal Osteodystrophy via Computational Analysis of Label-free Raman Detection of Multiple Biomarkers

“…Whereas both spectroscopic techniques provide a comprehensive chemical analysis that is useful for understanding likelihood of fractures and is complementary to that from QCT and MRI, relating to potentially in vivo translation, Raman spectroscopy is superior due to its insensitivity to water absorption. However, despites their accessibility, there are only relatively few reports on such Raman studies [15][16][17][18][19][20][21][22][23][24][25], with a slightly larger number of FT-IR investigations [26][27][28][29][30].…”

“…In a recent Raman spectroscopic study, we demonstrated that the bone samples of patients with ROD exhibit an overall increase in phenylalanine and decreases in calcium content, in mineral to matrix ratio, and in carbonate to matrix ratio [25]. Since just a single Raman spectrum is clearly not sufficient to assess at statistically significant levels the differences between normal and ROD samples, we took advantage of confocal Raman microscopy.…”