Gene-Activated Hyaluronic Acid-Based Cryogels for Cartilage Tissue Engineering
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Gene-Activated Hyaluronic Acid-Based Cryogels for Cartilage Tissue EngineeringAuthor(s)
Date
2023Citation
Carballo-Pedrares, N., López-Seijas, J., Miranda-Balbuena, D., Lamas, I., Yáñez, J., & Rey-Rico, A. (2023). Gene-activated hyaluronic acid-based cryogels for cartilage tissue engineering. Journal of Controlled Release, 362, 606-619. https://doi.org/10.1016/J.JCONREL.2023.09.008
Abstract
[Abstract] Articular cartilage injuries are very frequent lesions that if left untreated may degenerate into osteoarthritis. Gene transfer to mesenchymal stem cells (MSCs) provides a powerful approach to treat these lesions by promoting their chondrogenic differentiation into the appropriate cartilage phenotype. Non-viral vectors constitute the safest gene transfer tools, as they avoid important concerns of viral systems including immunogenicity and insertional mutagenesis. However, non-viral gene transfer usually led to lower transfection efficiencies when compared with their viral counterparts. Biomaterial-guided gene delivery has emerged as a promising alternative to increase non-viral gene transfer efficiency by achieving sustained delivery of the candidate gene into cellular microenvironment. In the present study, we designed hyaluronic acid-based gene-activated cryogels (HACGs) encapsulating a novel formulation of non-viral vectors based on niosomes (P80PX) to promote MSCs in situ transfection. The developed HACG P80PX systems showed suitable physicochemical properties to promote MSCs in situ transfection with very low cytotoxicity. Incorporation of a plasmid encoding for the transcription factor SOX9 (psox9) into HACG P80PX systems led to an effective MSCs chondrogenic differentiation with reduced expression of fibrocartilage and hypertrophic markers. The capacity of the developed systems to restore cartilage extracellular matrix was further confirmed in an ex vivo model of chondral defect.
Keywords
Cartilage repair
Gene therapy
Non-viral vectors
Niosomes
P80PX
Gene activated cryogel
HACG
Mesenchymal stem cells
Gene therapy
Non-viral vectors
Niosomes
P80PX
Gene activated cryogel
HACG
Mesenchymal stem cells
Description
Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG
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Creative Commons Attribution-Noncommercial-Noderivatives 4.0 International CC-BY-NC-ND