Photochemical Tissue Passivation (PTP) to Reduce Temporomandibular Joint (TMJ) Osteoarthritis (OA)

About This Grant

PROJECT SUMMARY/ABSTRACT Temporomandibular joint (TMJ) osteoarthritis (OA) is characterized by chronic inflammation, resulting in cartilage degradation and subchondral bone erosion, leading to jaw pain and a compromised quality of life. With no effective treatment currently available, there is a pressing need for new clinical approaches to the problem. Our innovative approach, which could potentially prevent the progression of TMJ-OA to more advanced stages, has the potential to reduce the need for complex and costly surgical procedures. Photocrosslinking tissue proteins (i.e., collagen) is a straightforward and clinically advantageous procedure. It involves applying an aqueous Rose Bengal (RB) solution to the tissue and exposure to green light. Protein crosslinking has been investigated for wound closure, anastomosis, nerve repair, and enhanced wound healing in many tissues. It has also been shown to reduce inflammatory responses in treated tissues, hence the term photochemical tissue passivation (PTP). Published data from our group shows that the network formed by extracellular protein crosslinking prevents inflammatory markers from infiltrating the treatment site. We also showed in rodent knee and shoulder models of fibrosis and post-traumatic arthritis that PTP reduces inflammation in the joint capsule. PTP was initially applied in other tissues by Dr. Redmond’s group. Only after collaborations with Dr. Guastaldi the leap was made to TMJ and this proposal. Dr. Redmond is a pioneer of photocrosslinking therapeutics, and Dr. Guastaldi has extensive experience with animal models, TMJ disease, and regeneration. We believe this innovative approach is only possible due to this partnership's unique combination of expertise. In addition, utilizing state-of-the-art optical diagnostic imaging techniques via Dr. Redmond’s and Dr. Guastaldi’s collaborators at the Wellman Center for Photomedicine (MGH) is another powerful and innovative step in assessing TMJ disease progression and therapeutic efficacy. Polarization- sensitive optical coherence tomography (PS-OCT) is an optical technique that has recently demonstrated the ability to measure cartilage fiber structure and orientation. Dr. Vakoc is a leader in the field of PS-OCT, and his lab is well-equipped to conduct rapid volumetric PS-OCT imaging. We propose to apply to the TMJ for the first time. The overall goal is to explore the potential of PTP to reduce inflammation and prevent the progression of TMJ-OA. A well-established rat model of TMJ-OA will be used to achieve this goal. We hypothesize that PTP of the TMJ capsule offers a promising, minimally invasive approach to halting TMJ-OA progression by reducing inflammation within the TMJ. The following specific aims will address the hypothesis: SA1) To assess the effect of PTP on the whole TMJ structure. PS-OCT imaging, micro-CT, histology, and pain assessment will assess the impact of PTP on the whole TMJ structure. SA2) To assess the efficacy of PTP to reduce TMJ-OA-related inflammation. Whole TMJ specimens tissues will undergo quantitative (Q-PCR) and qualitative (IHC staining) assessment for the presence of inflammatory markers.