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Raman needle arthroscopy for in vivo molecular assessment of cartilage

Research output: Contribution to journalArticlepeer-review

Kimberly R. Kroupa, Man I. Wu, Juncheng Zhang, Magnus Jensen, Wei Wong, Julie B. Engiles, Mark W. Grinstaff, Brian D. Snyder, Mads S. Bergholt, Michael B. Albro

Original languageEnglish
JournalJournal of Orthopaedic Research
Early online date18 Aug 2021
DOIs
Accepted/In press2021
E-pub ahead of print18 Aug 2021

Bibliographical note

Funding Information: The authors thank Dr. Thomas Schaer for assistance with in vivo ovine measures, Joshua Auger for assistance with procurement and processing of human cartilage specimens, and Sedat Dogru and Chenhao Yu for their assistance in implementing mechanical testing protocols. This study was supported by the Musculoskeletal Transplant Foundation (MTF) Biologics, the Arthritis Foundation, the 2020 Boston University Materials Science & Engineering Innovation Award, the Clare‐Booth Luce Scholars Program, the Boston University Undergraduate Research Opportunities Program, the Boston University College of Engineering Distinguished Summer Research Fellowship and Summer Term Alumni Research Scholars Program, and the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (Grant No. 802778). Publisher Copyright: © 2021 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

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 extracellular matrix (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 (SZ) COL anisotropy via a partial least squares–discriminant analysis-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 SZ COL 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 study advances Raman arthroscopy toward a transformative low-cost, minimally invasive diagnostic platform for objective monitoring of treatment outcomes from emerging OA therapies.

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