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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
dc.contributor.author | Madry, Henning | |
dc.contributor.author | Rey-Rico, Ana | |
dc.contributor.author | Venkatesan, Jagadeesh Kumar | |
dc.contributor.author | Schmitt, Gertrud | |
dc.contributor.author | Speicher-Mentges, Susanne | |
dc.contributor.author | Cucchiarini, Magali | |
dc.contributor.author | Goebel, Lars | |
dc.contributor.author | Zurakowski, David | |
dc.contributor.author | Laschke, Matthias W. | |
dc.contributor.author | Cai, Xiaoyu | |
dc.contributor.author | Menger, Michael D. | |
dc.contributor.author | Gao, Liang | |
dc.contributor.author | Müller-Brandt, Kathrin | |
dc.date.accessioned | 2024-07-10T15:08:49Z | |
dc.date.available | 2024-07-10T15:08:49Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | H. Madry, L. Gao, A. Rey-Rico, J. K. Venkatesan, K. Müller-Brandt, X. Cai, L. Goebel, G. Schmitt, S. Speicher-Mentges, D. Zurakowski, M. D. Menger, M. W. Laschke, M. Cucchiarini, 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. Adv. Mater. 2020, 32, 1906508. https://doi.org/10.1002/adma.201906508 | es_ES |
dc.identifier.uri | http://hdl.handle.net/2183/37893 | |
dc.description.abstract | [Abstract] 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. | es_ES |
dc.description.sponsorship | H.M. and L.G. contributed equally to this work. This project wassupported by the Deutsche Forschungsgemeinschaft (DFG RE 3828/2-1). All animal experiments were conducted in agreement with the nationallegislation on protection of animals and the National Institutes ofHealth (NIH) Guidelines for the Care and Use of Laboratory Animals(NIH Publication 85-23, Rev 1985) and were approved by the SaarlandUniversity Animal Committee according to German guidelines. | es_ES |
dc.description.sponsorship | Deutschland. Deutsche Forschungsgemeinschaft; DFG RE 3828/2-1 | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | WILEY-VCH | es_ES |
dc.relation.uri | https://doi.org/10.1002/adma.201906508 | es_ES |
dc.rights | Creative Commons Attribution CC BY 4.0 | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Biomaterial-guided therapy | es_ES |
dc.subject | Cartilage defects | es_ES |
dc.subject | Gene therapy | es_ES |
dc.subject | RAAV | es_ES |
dc.subject | Tissue engineering | es_ES |
dc.title | 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 | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.access | info:eu-repo/semantics/openAccess | es_ES |
UDC.journalTitle | Advanced Materials | es_ES |
UDC.volume | 32 | es_ES |
UDC.issue | 2 | es_ES |
UDC.startPage | Article 1906508 | es_ES |
dc.identifier.doi | 10.1002/adma.201906508 |