THU0464 Adhesive Barrier/Directional Controlled Release for Cartilage Repair by Endogenous Progenitor Cell Recruitment
Authors: G.-I. Im, J.-M. Lee, E.-A. Kim
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Implantation of the therapeutic depot is typical methods in tissue regeneration studies, but importantly, we developed an directional “releasing-to” approach by applying an adhesive gel patch (chitosan-catechol, CHI-C) on top of the fibrin gel, which plays a role in releasing the encapsulated PDGF-AA only to bone marrow direction for maximizing MSC cell migration. Furthermore, the migrated cells are retained on the defect site by the adhesive chitosan-catechol barrier. <h3>Objectives</h3> The purpose of this study is to introduce the concept of the adhesive barrier/directional controlled release and prove its efficacy through an <i>in vivo</i> tracking model. <h3>Methods</h3> 12 week-old male nude rats were anesthetized with zoletil and xylazine. A 1.5 mm outer diameter trephine drill was employed to create osteochondral defects (2.0×2.0 mm) in the trochlear groove of the femur. A hole was created inside the defect using a 26-gauge needle and deepened until blood gushed out. 1.0×10<sup>6</sup> MSCs suspended in 10 μl PBS was mixed with BD Matrigel of the same volume as described previously [1]. The mixture was then slowly injected into the marrow cavity. And then, the osteochondral defects were filling with PDGF-AA-loaded HCF and sealed once more with CHI-C adhesive. <h3>Results</h3> <i>In vivo</i> bioluminescence imaging was performed in transplanted animals for 14 days. In the HCF-only Group without PDGF-AA (Group 1), the majority of the injected MSCs remained in the marrow cavity for 7 days. On the other hand, Groups 2 (plugged with PDGF-AA-loaded HCF) and 3 (plugged with PDGF-AA and TGF-β1-loaded HCF) showed a time-dependent movement of injected cells toward the osteochondral defect. Interestingly, Group 4, in which osteochondral defects were sealed with CHI-C barrier, showed faster and greater movement of injected cells than other groups. Also, chemotactic potentials of Group 4 were maintained for 14 days while the cell migration was stopped within 7 days in other groups. On day 14, all the signals in Group 4 congregated at the osteochondral defect. After the animals were sacrificed at six week of transplantation, the femora were removed from the bodies and the far-red fluorescence signals were detected again. The fluorescent signals were detected in the osteochondral defect area in Groups 2, 3 and 4, whereas they were not detected in Group 1 (HCF-only Group). The total fluorescence signal in the femurs of Group 4 was 5.9-fold stronger than that of Group 1 (p&lt;0.05), 2.7-fold stronger than that of Group 2 (p&lt;0.05) and 2.5-fold stronger than that of Group 3 (p&lt;0.05). <h3>Conclusions</h3> We developed a novel system for osteochondral repair using directional bio-adhesive gel patch and growth factor-loaded HCF in which the CHI-C barrier induced a directional release of growth factors and blocked the dispersion of the migrated MSCs from the osteochondral bone region to other tissues. We confirmed that the CHI-C barrier enhanced the migration of MSCs to the osteochondral defect and induced better cartilage repair. This system is expected to make a significant contribution in cartilage tissue engineering without cell transplantation. <h3>References</h3> Lee JM, Kim BS, Lee H, Im GI. In vivo tracking of mesechymal stem cells using fluorescent nanoparticles in an osteochondral repair model. Mol Ther 2012:20:1434-42. <h3>Acknowledgements</h3> This study was supported by a grant from the National Research Foundation of Korea (2009-0092196). <h3>Disclosure of Interest</h3> None declared