Hydrogel-Guided, rAAV-Mediated IGF-I Overexpression Enables Long-Term Cartilage Repair and Protection against Perifocal Osteoarthritis in a Large-Animal Full-Thickness Chondral Defect Model at One Year In Vivo

Rey-Rico, AnaMadry, HenningVenkatesan, Jagadeesh KumarSchmitt, GertrudSpeicher-Mentges, SusanneCai, XiaoyuMeng, WeikunCucchiarini, MagaliMaihöfer, JohannaGoebel, LarsZurakowski, DavidMenger, Michael D.Laschke, Matthias W.2024-07-092024-07-092021J. Maihöfer, H. Madry, A. Rey-Rico, J. K. Venkatesan, L. Goebel, G. Schmitt, S. Speicher-Mentges, X. Cai, W. Meng, D. Zurakowski, M. D. Menger, M. W. Laschke, M. Cucchiarini, Hydrogel-Guided, rAAV-Mediated IGF-I Overexpression Enables Long-Term Cartilage Repair and Protection against Perifocal Osteoarthritis in a Large-Animal Full-Thickness Chondral Defect Model at One Year In Vivo. Adv. Mater. 2021, 33, 2008451. https://doi.org/10.1002/adma.202008451http://hdl.handle.net/2183/37847[Abstract] The regeneration of focal articular cartilage defects is complicated by the reduced quality of the repair tissue and the potential development of perifocal osteoarthritis (OA). Biomaterial-guided gene therapy may enhance cartilage repair by controlling the release of therapeutic sequences in a spatiotemporal manner. Here, the benefits of delivering a recombinant adeno-associated virus (rAAV) vector coding for the human insulin-like growth factor I (IGF-I) via an alginate hydrogel (IGF-I/AlgPH155) to enhance repair of full-thickness chondral defects following microfracture surgery after one year in minipigs versus control (lacZ/AlgPH155) treatment are reported. Sustained IGF-I overexpression is significantly achieved in the repair tissue of defects treated with IGF-I/AlgPH155 versus those receiving lacZ/AlgPH155 for one year and in the cartilage surrounding the defects. Administration of IGF-I/AlgPH155 significantly improves parameters of cartilage repair at one year relative to lacZ/AlgPH155 (semiquantitative total histological score, cell densities, matrix deposition) without deleterious or immune reactions. Remarkably, delivery of IGF-I/AlgPH155 also significantly reduces perifocal OA and inflammation after one year versus lacZ/AlgPH155 treatment. Biomaterial-guided rAAV gene transfer represents a valuable clinical approach to promote cartilage repair and to protect against OA.engCreative CommonsAttribution-NonCommercial-NoDerivs Licensehttp://creativecommons.org/licenses/by-nc-nd/3.0/es/Alginate hydrogelCartilage repairIGF-IPerifocal osteoarthritisRAAVHydrogel-Guided, rAAV-Mediated IGF-I Overexpression Enables Long-Term Cartilage Repair and Protection against Perifocal Osteoarthritis in a Large-Animal Full-Thickness Chondral Defect Model at One Year In Vivojournal articleopen access10.1002/adma.202008451