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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
Author(s) -
Madry Henning,
Gao Liang,
ReyRico Ana,
Venkatesan Jagadeesh K.,
MüllerBrandt Kathrin,
Cai Xiaoyu,
Goebel Lars,
Schmitt Gertrud,
SpeicherMentges Susanne,
Zurakowski David,
Menger Michael D.,
Laschke Matthias W.,
Cucchiarini Magali
Publication year - 2020
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.201906508
Subject(s) - materials science , in vivo , gene delivery , biomedical engineering , poloxamer , cartilage , genetic enhancement , biomaterial , viral vector , biophysics , recombinant dna , nanotechnology , biology , medicine , polymer , anatomy , gene , biochemistry , copolymer , composite material , microbiology and biotechnology
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‐h sox9 /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.