NovelKnees · Targeting Subchondral Bone Marrow Lesions, Microdamage and Remodelling using Novel Bisphosphonate-Loaded Delivery Systems to Prevent Post-Traumatic Osteoarthritis after Acute Knee Injury

Targeting Subchondral Bone Marrow Lesions, Microdamage and Remodelling using Novel Bisphosphonate-Loaded Delivery Systems to Prevent Post-Traumatic Osteoarthritis after Acute Knee Injury

The overall problem that was to be addressed by 'NovelKnees' was to “to understand why Anterior Cruciate Ligament (ACL) ruptures so frequently lead to PTOA, and determine the role of subchondral bone microdamage and BMLs in that process - and whether this can be harnessed for a new treatment strategy”. The proposed work is important for society since injury/disease of skeletal joints is a significant, and growing, problem among all age-groups (especially younger cohorts) and musculoskeletal isssues are a leading cause of pain and disability. Here, Objective 1 set out to determine the relationship between bone microdamage and joint disease that follows ACL rupture. We determined that a close relationship exists between these two things. Objective 2 was to determine the biological consequences of subchondral microdamage and Bone Marrow Lesions (BMLs) in term of localized pathological bone activity. We determined that localized increases in osteoclast activity occur in response to subchondral microdamage. Objective 3 was to develop an intra-articular drug-delivery system to target damaged subchondral bone via sustained release of therapeutic microparticles. We developed alginate based microparticles that successfully release bone targeting agents which reduce likelihood of PTOA development in model systems. This project set out to develop tissue-specific early intervention therapies to prevent PTOA after acute joint injury and to determine whether subchondral microdamage caused by ACL injury, increases remodeling which overlaps with BMLs, and stimulates a positive feedback-loop of catabolic events resulting in PTOA via bone- cartilage crosstalk. In conclusion, this action demonstrated that sustained release of bisphosphonates in a suitable carrier can cross the osteochondral junction to inhibit bone remodelling and the catabolic cycle in cartilage and thus has potential to prevent PTOA. This goal was achieved through the development of bone targeting treatment system used in a preclinical joint injury system.

Data: CORDIS, © European Union