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.
Animals
Cartilage, Articular
/ metabolism
Dependovirus
/ genetics
Drug Carriers
/ chemistry
Drug Liberation
Genetic Therapy
Genetic Vectors
/ chemistry
Hydrogels
/ chemistry
Models, Molecular
Molecular Conformation
Poloxamer
/ chemistry
Polyethylene Glycols
/ chemistry
Propylene Glycols
/ chemistry
Swine
Temperature
biomaterial-guided therapy
cartilage defects
gene therapy
rAAV
tissue engineering
Journal
Advanced materials (Deerfield Beach, Fla.)
ISSN: 1521-4095
Titre abrégé: Adv Mater
Pays: Germany
ID NLM: 9885358
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
04
10
2019
pubmed:
26
11
2019
medline:
18
11
2020
entrez:
26
11
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31763733
doi: 10.1002/adma.201906508
doi:
Substances chimiques
Drug Carriers
0
Hydrogels
0
PEO-PPO-PEO
0
Propylene Glycols
0
Poloxamer
106392-12-5
Polyethylene Glycols
3WJQ0SDW1A
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1906508Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : RE 3828/2-1
Informations de copyright
© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Références
A. Guermazi, D. Hayashi, F. W. Roemer, J. Niu, E. K. Quinn, M. D. Crema, M. C. Nevitt, J. Torner, C. E. Lewis, D. T. Felson, Arthritis Rheumatol. 2017, 69, 560.
J. M. Hootman, C. G. Helmick, Arthritis Rheum. 2006, 54, 226.
T. D. Brown, R. C. Johnston, C. L. Saltzman, J. L. Marsh, J. A. Buckwalter, J. Orthop. Trauma 2006, 20, 739.
M. Cucchiarini, H. Madry, Nat. Rev. Rheumatol. 2019, 15, 18.
C. Alvarez-Lorenzo, A. Rey-Rico, A. Sosnik, P. Taboada, A. Concheiro, Front. Biosci. 2010, E2, 424.
K. T. Oh, T. K. Bronich, A. V. Kabanov, J. Controlled Release 2004, 94, 411.
P. Diaz-Rodriguez, A. Rey-Rico, H. Madry, M. Landin, M. Cucchiarini, Int. J. Pharm. 2015, 496, 614.
A. Rey-Rico, J. Frisch, J. K. Venkatesan, G. Schmitt, I. Rial-Hermida, P. Taboada, A. Concheiro, H. Madry, C. Alvarez-Lorenzo, M. Cucchiarini, ACS Appl. Mater. Interfaces 2016, 8, 20600.
A. Rey-Rico, J. K. Venkatesan, G. Schmitt, S. Speicher-Mentges, H. Madry, M. Cucchiarini, Mol. Pharmaceutics 2018, 15, 2816.
A. Rey-Rico, J. K. Venkatesan, G. Schmitt, A. Concheiro, H. Madry, C. Alvarez-Lorenzo, M. Cucchiarini, Int. J. Nanomed. 2017, 12, 6985.
A. Rey-Rico, J. K. Venkatesan, J. Frisch, I. Rial-Hermida, G. Schmitt, A. Concheiro, H. Madry, C. Alvarez-Lorenzo, M. Cucchiarini, Acta Biomater. 2015, 27, 42.
P. Orth, C. Peifer, L. Goebel, M. Cucchiarini, H. Madry, Prog. Histochem. Cytochem. 2015, 50, 19.
L. Goebel, P. Orth, A. Muller, D. Zurakowski, A. Bucker, M. Cucchiarini, D. Pape, H. Madry, Osteoarthritis Cartilage 2012, 20, 1046.
L. A. Fortier, H. O. Mohammed, G. Lust, A. J. Nixon, J. Bone Jt. Surg., Br. Vol. 2002, 84-B, 276.
K. Tao, J. Frisch, A. Rey-Rico, J. K. Venkatesan, G. Schmitt, H. Madry, J. Lin, M. Cucchiarini, Stem Cell Res. Ther. 2016, 7, 20.
M. Cucchiarini, P. Orth, H. Madry, J. Mol. Med. 2013, 91, 625.
S. A. Rodeo, A. Seneviratne, K. Suzuki, K. Felker, T. L. Wickiewicz, R. F. Warren, J. Bone Jt. Surg., Am. Vol. 2000, 82, 1071.
a) C. H. Evans, S. C. Ghivizzani, T. A. Oligino, P. D. Robbins, Arthritis Res. 2001, 3, 142;
b) D. Bellavia, F. Veronesi, V. Carina, V. Costa, L. Raimondi, A. De Luca, R. Alessandro, M. Fini, G. Giavaresi, Cell. Mol. Life Sci. 2018, 75, 649.
Q. Meng, S. An, R. A. Damion, Z. Jin, R. Wilcox, J. Fisher, A. Jones, J. Mech. Behav. Biomed. Mater. 2017, 65, 439.
A. Chevrier, C. D. Hoemann, J. Sun, M. D. Buschmann, Osteoarthritis Cartilage 2011, 19, 136.
P. Orth, H. Madry, Tissue Eng., Part B 2015, 21, 504.
L. Gao, P. Orth, L. K. Goebel, M. Cucchiarini, H. Madry, Sci. Rep. 2016, 6, 32982.
L. Gao, P. Orth, K. Muller-Brandt, L. K. Goebel, M. Cucchiarini, H. Madry, Sci. Rep. 2017, 7, 45189.
a) J. R. Steadman, W. G. Rodkey, J. J. Rodrigo, Clin. Orthop. Relat. Res. 2001, 391, S362;
b) H. Madry, L. Gao, H. Eichler, P. Orth, M. Cucchiarini, Stem Cells Int. 2017, 2017, 1609685.
N. Ashammakhi, S. Ahadian, M. A. Darabi, M. El Tahchi, J. Lee, K. Suthiwanich, A. Sheikhi, M. R. Dokmeci, R. Oklu, A. Khademhosseini, Adv. Mater. 2019, 31, 1804041.