Biomimetic aggrecan molecularly engineers articular cartilage following intra-articular injection in an OA rabbit model in vivo: a pilot study

Event Abstract Back to Event Biomimetic aggrecan molecularly engineers articular cartilage following intra-articular injection in an OA rabbit model in vivo: a pilot study Evan Phillips1, Diego Galindo1, Mickey Bui2, Richard Huneke2, Emily Reimold2, Adam Taylor2, Katsiaryna Prudnikova1, Michele Marcolongo1 and Mary Mulcahey2 1 Drexel University, Materials Science, United States 2 Drexel University, College of Medicine, United States Introduction: Several biomolecules are depleted in osteoarthritis (OA) including hyaluronic acid (HA) in the synovial fluid and aggrecan in articular cartilage. Intra-articular HA injections have been widely used in an attempt to restore joint lubrication and reduce cartilage erosion, however they have had limited success[1]. Our lab has synthesized a novel biomimetic aggrecan (BA) aimed to infiltrate and distribute in articular cartilage delivered via an intra-articular injection[2]. BA mimics the 3-D bottle brush structure and properties of naturally occurring aggrecan and consists of a poly(acrylic acid) (10kDa) core with chondroitin sulfate bristles. BA is intended to restore hydration and mechanical function to arthritic cartilage by molecularly engineering tissue without relying on cellular synthesis to regenerate the extracellular matrix. Here we investigate the effect of intra-articular injections of BA into normal and arthritic rabbit knee joints by determining the histological response of articular cartilage to BA and quantifying the coefficient of friction of the rabbit knee joint. Materials and Methods: ACL Transection (ACLT) was used to create osteoarthritis in the right hindlimb of 4 female New Zealand white rabbits while the left hindlimb served as a control (IACUC approved pilot study). These rabbits formed 2 groups: 1) ACLT and 2) ACLT + BA. Five weeks after surgery, the two rabbits in the ACLT+ BA group underwent weekly injections of BA for 3 weeks. Two additional non-ACLT rabbits underwent BA injections in the right hindlimb once weekly for 3 weeks. The contralateral hindlimb of these two rabbits had one injection of fluorescently-labeled BA two days prior to sacrifice. Immediately after euthanasia, the limbs were tested in a custom pendulum friction tester to measure joint friction and then prepared for histology or fluorescent imaging. Results: Osteoarthritic rabbit knees treated with BA exhibited a lower coefficient of friction than OA knees alone. The rabbit knees which only received BA injections exhibited almost the same coefficient as the control knees. A more robust articular cartilage layer is present in arthritic specimens treated with BA than arthritic specimens with no treatment. Confocal microscopy of fluorescently labeled BA injected knees showed fluorescence within the articular cartilage. Discussion: The results from our pilot study provide preliminary data to support the ability of biomimetic aggrecan to molecularly engineer osteoarthritic cartilage through infiltration of BA from the synovial joint into the articular cartilage layer. BA has implications not only for mechanical restoration of the joint, but also for localized drug delivery to cartilage. Our preliminary findings on joint friction indicate that BA has no adverse effect on joint coefficient of friction and may help to reverse the increased friction that resulted from OA. A study using the same model is currently underway with a group size of five. Conclusion: Our pilot results indicate that BA decreases the coefficient of friction of the osteoarthritic knee and increases the cellularity and thickness of the articular cartilage, supporting our hypothesis that BA can provide increased hydration to the joint and regenerate superficial layers of articular cartilage. We would like to thank the Clinical and Translational Research Institute at Drexel for funding this projectReferences:[1] Evidence Based Guideline, 2d Edition: Summary of Recommendation for the Treatment of Osteoarthritis of the Knee. AAOS; 2013.[2] Prudnikova, K. et al. (2013) Novel Biomimetic Proteoglycans for Molecular Engineering of Degenerated Tissue. in Society for Biomaterials Boston, MA. Keywords: Extracellular Matrix, Regenerative Medicine, in vivo, Biomimetic Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: General Session Oral Topic: Biomaterials evaluation in animal models Citation: Phillips E, Galindo D, Bui M, Huneke R, Reimold E, Taylor A, Prudnikova K, Marcolongo M and Mulcahey M (2016). Biomimetic aggrecan molecularly engineers articular cartilage following intra-articular injection in an OA rabbit model in vivo: a pilot study. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02748 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Evan Phillips Diego Galindo Mickey Bui Richard Huneke Emily Reimold Adam Taylor Katsiaryna Prudnikova Michele Marcolongo Mary Mulcahey Google Evan Phillips Diego Galindo Mickey Bui Richard Huneke Emily Reimold Adam Taylor Katsiaryna Prudnikova Michele Marcolongo Mary Mulcahey Google Scholar Evan Phillips Diego Galindo Mickey Bui Richard Huneke Emily Reimold Adam Taylor Katsiaryna Prudnikova Michele Marcolongo Mary Mulcahey PubMed Evan Phillips Diego Galindo Mickey Bui Richard Huneke Emily Reimold Adam Taylor Katsiaryna Prudnikova Michele Marcolongo Mary Mulcahey Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.