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

• Published in: Advanced materials (Weinheim) Vol. 33; no. 16; pp. e2008451 - n/a
• Main Authors: Maihöfer, Johanna, Madry, Henning, Rey‐Rico, Ana, Venkatesan, Jagadeesh K., Goebel, Lars, Schmitt, Gertrud, Speicher‐Mentges, Susanne, Cai, Xiaoyu, Meng, Weikun, Zurakowski, David, Menger, Michael D., Laschke, Matthias W., Cucchiarini, Magali
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.04.2021
• Subjects: alginate hydrogel; Alginates; Arthritis; Biomedical materials; Cartilage; cartilage repair; Defects; Gene therapy; Growth factors; Hydrogels; IGF‐I; Insulin; Materials science; Microfracture; Osteoarthritis; perifocal osteoarthritis; rAAV; Regeneration; Thickness; rAAV; IGF-I; alginate hydrogel; cartilage repair; perifocal osteoarthritis
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.202008451

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. Alginate‐hydrogel‐guided delivery of a recombinant adeno‐associated virus vector coding for a human insulin‐like growth factor I (IGF‐I) gene sequence (IGF‐I/AlgPH155) safely enhances the repair of full‐thickness chondral defects and reduces perifocal osteoarthritis and inflammation in minipigs in vivo over one year via effective IGF‐I overexpression relative to control (reporter lacZ/AlgPH155) vector delivery.