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

© 2021 The Authors. Advanced Materials published by Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 33(2021), 16 vom: 04. Apr., Seite e2008451
1. Verfasser: Maihöfer, Johanna (VerfasserIn)
Weitere Verfasser: 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: Online-Aufsatz
Sprache:English
Veröffentlicht: 2021
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article IGF-I alginate hydrogel cartilage repair perifocal osteoarthritis rAAV Insulin-Like Growth Factor I 67763-96-6 Hydrogels Alginates
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245 1 0 |a 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 
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520 |a 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 
650 4 |a Journal Article 
650 4 |a IGF-I 
650 4 |a alginate hydrogel 
650 4 |a cartilage repair 
650 4 |a perifocal osteoarthritis 
650 4 |a rAAV 
650 7 |a Insulin-Like Growth Factor I  |2 NLM 
650 7 |a 67763-96-6  |2 NLM 
650 7 |a Hydrogels  |2 NLM 
650 7 |a Alginates  |2 NLM 
700 1 |a Madry, Henning  |e verfasserin  |4 aut 
700 1 |a Rey-Rico, Ana  |e verfasserin  |4 aut 
700 1 |a Venkatesan, Jagadeesh K  |e verfasserin  |4 aut 
700 1 |a Goebel, Lars  |e verfasserin  |4 aut 
700 1 |a Schmitt, Gertrud  |e verfasserin  |4 aut 
700 1 |a Speicher-Mentges, Susanne  |e verfasserin  |4 aut 
700 1 |a Cai, Xiaoyu  |e verfasserin  |4 aut 
700 1 |a Meng, Weikun  |e verfasserin  |4 aut 
700 1 |a Zurakowski, David  |e verfasserin  |4 aut 
700 1 |a Menger, Michael D  |e verfasserin  |4 aut 
700 1 |a Laschke, Matthias W  |e verfasserin  |4 aut 
700 1 |a Cucchiarini, Magali  |e verfasserin  |4 aut 
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773 1 8 |g volume:33  |g year:2021  |g number:16  |g day:04  |g month:04  |g pages:e2008451 
856 4 0 |u http://dx.doi.org/10.1002/adma.202008451  |3 Volltext 
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