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.
IGF-I
alginate hydrogel
cartilage repair
perifocal osteoarthritis
rAAV
Journal
Advanced materials (Deerfield Beach, Fla.)
ISSN: 1521-4095
Titre abrégé: Adv Mater
Pays: Germany
ID NLM: 9885358
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
revised:
02
02
2021
received:
15
12
2020
pubmed:
19
3
2021
medline:
28
10
2021
entrez:
18
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33734514
doi: 10.1002/adma.202008451
doi:
Substances chimiques
Hydrogels
0
Insulin-Like Growth Factor I
67763-96-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2008451Subventions
Organisme : The Gene Therapy Center, University of North Carolina
Organisme : Division of Experimental Medicine
Organisme : Harvard Institutes of Medicine and Beth Israel Deaconess Medical Center
Informations de copyright
© 2021 The Authors. Advanced Materials published by Wiley-VCH GmbH.
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