Biology subjects

Snyder, B. D.

Publications and source records attributed to Snyder, B. D..

4 recordsLinked to original sources

bioRxiv2026

Raman-probe-derived biomarkers account for cartilage composition, structure, and viscoelastic properties

Raman spectroscopy is an inelastic light scattering technique that reflects the vibrational modes of the biochemical building blocks of the major constituents that comprise the cartilage extracellular matrix (ECM): glycosaminoglycans (GAG), type-II collagen (COL), and water. We investigated whether ECM-specific biomarkers measured with our recently developed arthroscopy-compatible Raman needle probe characterize the functional viscoelastic properties of articular cartilage explants. Equine osteochondral explants were harvested from high-load (femoral condyle) and low-load (intertrochlear groove) sites to evaluate Raman-derived biomarkers of cartilage structure and function. Viscoelastic material properties (equilibrium/dynamic modulus, phase shift) were determined by mechanical indentation. A computational fibril-reinforced biphasic material model was used to estimate the glycosaminoglycan-associated non-fibrillar-matrix modulus, the collagen-associated fibril-network modulus, and hydraulic permeability. Raman-derived biomarkers enabled evaluation of cartilage tissue composition and structure, accounting for 81% of the variation in GAG content, 53% of the variation in COL content, and 58% of the variation in COL anisotropy. Biomarkers also accounted for 81% of the variation in equilibrium modulus, 58% in dynamic modulus, and 51% in phase shift. For poroelastic properties, biomarkers accounted for 83% of the variation in non-fibrillar-matrix modulus, 25% of the variation in fibril-network modulus, and 34% of the variation in hydraulic permeability. Clinical Significance: Raman spectroscopy provides objective compositional biomarkers that account for viscoelastic material properties underlying articular cartilage function. These findings support its future use as an arthroscopic platform for objective assessment of cartilage injury, monitoring of disease progression, and evaluation of therapeutic interventions.

bioengineering↗

bioRxiv2026

Arthroscopic Raman Probe Provides Biomarkers of TMJ Tissue Composition that Account for Tissue Function

Background: Temporomandibular joint (TMJ) disorders affect up to 25% of the population and may require diverse surgical interventions. However, intraoperative decision-making relies largely on visual assessment, which does not quantitatively characterize tissue composition or mechanical function. Raman spectroscopy offers a nondestructive approach to molecular-level tissue characterization, but its application to TMJ tissues remains unvalidated. Methods: An arthroscopy-compatible Raman probe was used to characterize mandibular condyles (n=15 porcine, n=11 human) and human articular discs (n=7). Raman-derived biomarkers associated with glycosaminoglycans (GAG), collagen (COL), water (H2O), and hydroxyapatite (HA) were evaluated against condylar indentation modulus and disc tensile modulus. Arthroscopic measurements in cadaveric TMJs assessed technical feasibility, while hyperspectral Raman imaging characterized spatial compositional distributions. Results: For condylar cartilage, combined GAG and H2O biomarkers accounted for 86% of the variation in indentation modulus (R2=0.86), compared with 4% for Outerbridge grading (R2=0.04). For articular discs, combined proline and water-associated biomarkers accounted for 88% of the variation in tensile modulus (R2=0.88). Raman spectra acquired in situ under simulated arthroscopic conditions were comparable in quality to ex vivo measurements. Raman imaging revealed distinct compositional patterns in healthy and degenerated tissues, including GAG depletion and cartilage thinning in degenerated condylar cartilage. Conclusions: Raman-derived biomarkers are strongly associated with TMJ cartilage and disc mechanical properties and outperform Outerbridge grading in explaining variation in condylar indentation modulus. Arthroscopic Raman spectroscopy is technically feasible and may complement visual assessment by providing objective compositional information to support future development of tissue-informed surgical decision-making.

pathology↗

bioRxiv2026

Absolute Quantification of Tissue Composition by Raman Spectroscopy

Raman spectroscopy captures the molecular fingerprints of living tissues without labels or tissue destruction. Translating these spectra into absolute measures of tissue biochemical composition remains a challenge owing to tissue-dependent optical properties, variations in sampling volume, and lack of normalization standards requisite for quantitative scaling. Here we introduce a scheme to derive the biochemical constituents of a tissue expressed as a percentage of the tissue wet weight, like biochemical assays, from Raman spectra measured optically. Nonlinear polynomial models of Raman spectra are trained on chemically defined phantoms that mimic the variability of the essential biochemical constituents of a tissue, accommodating spectral overlap and tissue-dependent optical effects. We validated this scheme using cartilage, a tissue fundamental to diarthrodial joint function. Cartilage is comprised of glycosaminoglycans, collagens and water that act synergistically to impart the rheological and tribological material properties essential to tissue function. Using biochemically perturbed live cartilage explants, phantom-calibrated Raman spectroscopy (PC-Raman) resolved constituent-specific changes and achieved quantitative agreement with independent biochemical assays (R-squared = 0.88-0.92; slopes {approx} 1.0; 95% confidence intervals {+/-}2.7-3.2%pt). We demonstrate that PC-Raman is applicable across the hierarchy of tissue interrogation from microscopic imaging of tissue extracellular matrix composition to macroscopic longitudinal monitoring of drug effects in-vitro using live tissue constructs and in-vivo assessments of cartilage regeneration in an equine cartilage repair model. Converting Raman spectra measurements of the essential biochemical constituents of a tissue in absolute terms (tissue wet-weight-%) allows for the non-destructive, longitudinal quantification of tissue composition in disease (tissue degeneration) and in response to treatment (tissue repair).

biochemistry↗

bioRxiv2021

Raman Needle Arthroscopy for In Vivo Molecular Assessment of Cartilage

The development of treatments for osteoarthritis (OA) is burdened by the lack of standardized biomarkers of cartilage health that can be applied in clinical trials. We present a novel arthroscopic Raman probe that can "optically biopsy" cartilage and quantify key ECM biomarkers for determining cartilage composition, structure, and material properties in health and disease. Technological and analytical innovations to optimize Raman analysis include: 1) multivariate decomposition of cartilage Raman spectra into ECM-constituent-specific biomarkers (glycosaminoglycan [GAG], collagen [COL], water [H2O] scores), and 2) multiplexed polarized Raman spectroscopy to quantify superficial zone collagen anisotropy via a PLS-DA-derived Raman collagen alignment factor (RCAF). Raman measurements were performed on a series of ex vivo cartilage models: 1) chemically GAG-depleted bovine cartilage explants (n=40), 2) mechanically abraded bovine cartilage explants (n=30), 3) aging human cartilage explants (n=14), and 4) anatomical-site-varied ovine osteochondral explants (n=6). Derived Raman GAG score biomarkers predicted 95%, 66%, and 96% of the variation in GAG content of GAG-depleted bovine explants, human explants, and ovine explants, respectively (p<0.001). RCAF values were significantly different for explants with abrasion-induced superficial zone collagen loss (p<0.001). The multivariate linear regression of Raman-derived ECM biomarkers (GAG and H2O scores) predicted 94% of the variation in elastic modulus of ovine explants (p<0.001). Finally, we demonstrated the first in vivo Raman arthroscopy assessment of an ovine femoral condyle through intraarticular entry into the synovial capsule. This work advances Raman arthroscopy towards a transformative low cost, minimally invasive diagnostic platform for objective monitoring of treatment outcomes from emerging OA therapies.

bioengineering↗