Use of a prostaglandin analog to improve blood flow and tendon regeneration in a rabbit model

Tendon and ligament injuries account for 30% of all musculoskeletal consultations with 4 million new incidences worldwide each year. Current medical treatments, such as NSAIDS, Corticosteroids and injection of biologics and surgical remedies often fall short in restoring optimal tendon function, leading to elevated medical costs, prolonged recovery and significant productivity loss. Mature tendons are characterized by their dense structure and reduced vascularization, resulting in protracted healing times. Accelerating the healing process and enhancing regeneration can be achieved by augmenting blood circulation, thus facilitating the delivery of essential oxygen and nutrients while aiding in the clearance of fluid build-up. This research focuses on promoting patellar tendon repair by inducing vasodilation, using a localized injection of an FDA-approved small molecule drug in the knee to improve blood flow and accelerate regeneration. In this 10 weeks in vivo study, we pursue two primary objectives with eight white New Zealand rabbits, divided into a control group and a study group, both subjected to a surgical procedure to induce a right patellar tendon injury. While the control group receives weekly saline injections, the study group is treated with the drug under investigation. The first objective is to optimize 7T magnetic resonance (MR) sequences for the image acquisition of the rabbit patellar tendon under a significant constraint: completing all scans within an hour to ensure the animals' well-being. This limitation makes it challenging to achieve sufficient resolution and an excellent signal-to-noise ratio while accommodating all intended acquisitions. The acquired images, taken bi-weekly, are instrumental in generating parametric maps that quantify the tendon's healing process using T1, T2 and dynamic contrast enhanced (DCE) sequences. Our second objective is to craft a specialized MATLAB code and develop a user interface to facilitate the analysis of these images, which involves image uploading, segmentation, parametric map computation and quantitative data extraction. The next phase of this project involves micro-CT and histological analyses to quantify osteophytes in the post-injury knee and assess fibrotic tissue development in the tendon; these analyses provide a cellular view of tendon repair and drug effects. Future plans also include broadening our study to larger sample sizes and varied animal models, exploring the effects on different tendons and delving into alternative drug combinations or delivery methods to optimize tendon recovery.