MSE Innovation Grant Program

Articular cartilage is made up of a mechanically robust extracellular matrix (ECM) consisting of a dense content of glycosaminoglycans (GAG) interspersed within an organized fibrous network of type-II collagen (COL). During osteoarthritis (OA), degeneration of these constituents occurs in stages. Early stage degeneration (OARSI grade 0-2) is marked by difficult-to-detect tissue changes: notably, an initial loss of GAG from the topmost layers of the cartilage (Fig 1). This is followed by far more substantial degeneration, marked by the progressive physical erosion of the cartilage matrix until bone-on-bone contact is reached. There is a growing consensus that the early stage of the disease, before substantial tissue erosion has occurred, may represent a critical clinical window, when intervention strategies (e.g., biologics, viscosupplementation, physical therapy, lifestyle changes) may be most effective at delaying or reversing the onset of cartilage degeneration. However, the ability to diagnose cartilage degeneration in early-stage OA remains a considerable clinical challenge, as state-of-the-art imaging modalities are predominantly suited for diagnosing later stages of OA.

Raman spectroscopy is an inelastic light scattering technique with a unique potential to monitor the key degenerative changes that occur in early OA. This technique yields distinct spectra based on a tissue’s precise molecular vibrational bonds. Accordingly, it can achieve label-free assessments of biochemical composition with a remarkably high degree of molecular specificity. In this proposal, we start to bring the promise of Raman-based OA diagnostics into a clinical reality. Here, we build upon our recent work on Raman-based cartilage ECM measurements 1-4 and develop a novel intra-articular needle-based Raman probe to diagnose early OA (Fig 2). This can achieve the first ever assessment of surface GAG depletion, the major biochemical degenerative change associated with early OA. The platform adopts key technological and analytical innovations that are optimized for clinical early-OA diagnostics, including: 1) a lens-based needle probe tip for surface-targeted Raman measurements (where early OA is most prominent), and 2) multivariate statistical algorithms to quantify GAG content. The platform is minimally invasive, label free, and low cost. Intra-articular Raman spectroscopy can serve as a transformative diagnostic platform, offering highly accurate biochemical assessments of early OA. This system can serve as: 1) a clinical and pre-clinical research tool to lead the identification of novel OA therapeutics, and 2) an outpatient-based, real-time diagnostic platform to guide early OA treatment courses. This project aims examine the diagnostic potential of Raman spectroscopy via assessments of ex vivo articular cartilage specimens. The data collected in this project will serve as a foundation for exciting future investigations of Raman diagnostics on expanded ex vivo data sets and in vivo OA models.

Project collaborator: Dr. Mads Bergholt; Kings College London