A sustained release gene delivery system based on polymerosome-entrapped injectable hydrogel for articular cartilage tissue engineering: a hypothetical approach
DOI:
https://doi.org/10.22034/JATE.2018.26Keywords:
Osteoarthritis; Gene therapy; Injectable hydrogel; Sustained release, PolymerosomeAbstract
Nowadays, Osteoarthritis (OA) is the main cause of disability, which is incurable, costly and responds poorly to treatment. Besides the common treatments, gene-activated scaffolds serve as new approach in the cartilage regenerative medicine. This hypothesis discusses a strategy for treating OA by combination of gene sustained release and tissue engineering. Possible intra-articular sites of gene transfer include the synovium and the cartilage. Most of experimental progresses have been made with gene transfer to the synovium, using viral and non-viral vectors. The studies mainly have been focused on in-vivo and ex-vivo transfer of therapeutic genes, which overexpress synthesis of the cartilaginous matrix, or inhibit its breakdown. Insulin like growth factor-1 (IGF-1) is an important growth factor for cartilage homeostasis, which leads to increase synthesis of the matrix macromolecules, decrease the catabolism of these molecules, serves as a chondrocyte survival factor and promote expression of the cartilaginous phenotype. Interleukin-1 (IL-1) known as a key mediator of cartilage loss in OA, and therefore, IL-1 receptor antagonist (IL-1Ra) gene transfer showed the therapeutic effects in experimental models of OA. Here, we argue the potential of intra-articular IGF-1 and IL-1Ra gene transfer in OA. As a scaffold delivering therapeutic genes, we hypothesized an alginate sulfate injectable hydrogel for sustained release of polymerosome, as gene carrier, for localized gene delivery in the articular cartilage defects.
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