Nanofibrous spongy microspheres to deliver rabbit mesenchymal stem cells and anti-miR-199a to regenerate nucleus pulposus and prevent calcification.
Biomaterials
; 256: 120213, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32736170
ABSTRACT
Lower back pain is mainly caused by intervertebral disc degeneration, in which calcification is frequently involved. Here novel nanofibrous spongy microspheres (NF-SMS) are used to carry rabbit bone marrow mesenchymal stromal cells (MSCs) to regenerate nucleus pulposus tissues. NF-SMS are shown to significantly enhance the MSC seeding, proliferation and differentiation over control microcarriers. Furthermore, a hyperbranched polymer (HP) with negligible cytotoxicity and high microRNA (miRNAs) binding affinity is synthesized. The HP can complex with anti-miR-199a and self-assemble into "double shell" polyplexes which are able to achieve high transfection efficiency into MSCs. A double-emulsion technique is used to encapsulate these polyplexes in biodegradable nanospheres (NS) to enable sustained anti-miR-199 delivery. Our results demonstrate that MSC/HP-anti-miR-199a/NS/NF-SMS constructs can promote the nucleus pulposus (NP) phenotype and resist calcification in vitro and in a subcutaneous environment. Furthermore, injection of MSC/HP-anti-miR-199a/NS/NF-SMS can stay in place, produce functional extracellular matrix, maintain disc height and prevent intervertebral disc (IVD) calcification in a rabbit lumbar degeneration model.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Degeneração do Disco Intervertebral
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Nanofibras
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Células-Tronco Mesenquimais
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Núcleo Pulposo
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Disco Intervertebral
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article