Using redox balance to guide surgical and therapeutic decisions for cartilage disease - PROJECT SUMMARY/ABSTRACT
The goal of this research project is to develop optical redox imaging (ORI)-based medical instruments to guide
surgical and therapeutic approaches in early cartilage damage. Osteoarthritis (OA), for which cartilage pathology
is a central aspect, remains a challenging clinical problem without disease-modifying therapeutic strategies. This
challenge is exacerbated by the inability of current diagnostic methods to accurately classify cartilage damage
early in the OA disease process.
Redox imbalance occurs in the OA disease process. Mitochondrial dysfunction is of particular importance,
occurring in OA and after traumatic injury. Therapeutic strategies that target mitochondrial dysfunction and
metabolic imbalance to treat OA show potential for modifying the disease trajectory. Therefore, measuring
cartilage metabolic imbalance has strong potential for early OA diagnosis and for evaluating therapeutic
strategies.
This research program will use ORI as a diagnostic and evaluative tool for OA. ORI is a label-free, real-time
method that captures the autofluorescence of electron donors and an electron acceptor, thereby providing insight
into the metabolic balance of a tissue. ORI has been used in the cancer field to identify organoid responses to
treatments and distinguish cell subgroups, thus suggesting its utility as a diagnostic and screening tool. Our
preliminary data demonstrate that ORI metrics in cartilage are mechanoresponsive, oxygen sensitive, and are
correlated with pathology. We will extend our preliminary data to further develop ORI as a tool to diagnose
metabolic imbalances associated with pathology and evaluate emerging therapeutic strategies in cartilage.
This proposal includes three aims. In Aim 1, we will develop a stress test that can be used to diagnose cartilage
disease based on changes in ORI metrics following a mechanical stimulus. In Aim 2, we will develop an ex vivo
test platform to rapidly evaluation emergent therapeutic strategies. In Aim 3, we will develop a medical instrument
that captures ORI for staging cartilage disease. At the conclusion of this research, we will have developed ORI
as an instrument to diagnose cartilage pathology, investigated ORI as a platform to test interventions, and
generated a preliminary arthroscopy medical instrument ready for clinical translation.
