Thermosensitive Hydrogel Based on PEO-PPO-PEO Poloxamers for a Controlled In Situ Release of Recombinant Adeno-Associated Viral Vectors for Effective Gene Therapy of Cartilage Defects

Thermosensitive Hydrogel Based on PEO-PPO-PEO Poloxamers for a Controlled In Situ Release of Recombinant Adeno-Associated Viral Vectors for Effective Gene Therapy of Cartilage Defects

© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 32(2020), 2 vom: 20. Jan., Seite e1906508
1. Verfasser: Madry, Henning (VerfasserIn)
Weitere Verfasser: Gao, Liang, Rey-Rico, Ana, Venkatesan, Jagadeesh K, Müller-Brandt, Kathrin, Cai, Xiaoyu, Goebel, Lars, Schmitt, Gertrud, Speicher-Mentges, Susanne, Zurakowski, David, Menger, Michael D, Laschke, Matthias W, Cucchiarini, Magali
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2020
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article biomaterial-guided therapy cartilage defects gene therapy rAAV tissue engineering Drug Carriers Hydrogels PEO-PPO-PEO Propylene Glycols mehr... Poloxamer 106392-12-5 Polyethylene Glycols 3WJQ0SDW1A
Beschreibung
Zusammenfassung:© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Advanced biomaterial-guided delivery of gene vectors is an emerging and highly attractive therapeutic solution for targeted articular cartilage repair, allowing for a controlled and minimally invasive delivery of gene vectors in a spatiotemporally precise manner, reducing intra-articular vector spread and possible loss of the therapeutic gene product. As far as it is known, the very first successful in vivo application of such a biomaterial-guided delivery of a potent gene vector in an orthotopic large animal model of cartilage damage is reported here. In detail, an injectable and thermosensitive hydrogel based on poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO)-PEO poloxamers, capable of controlled release of a therapeutic recombinant adeno-associated virus (rAAV) vector overexpressing the chondrogenic sox9 transcription factor in full-thickness chondral defects, is applied in a clinically relevant minipig model in vivo. These comprehensive analyses of the entire osteochondral unit with multiple standardized evaluation methods indicate that rAAV-FLAG-hsox9/PEO-PPO-PEO hydrogel-augmented microfracture significantly improves cartilage repair with a collagen fiber orientation more similar to the normal cartilage and protects the subchondral bone plate from early bone loss
Beschreibung:Date Completed 16.11.2020
Date Revised 16.11.2020
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.201906508