A sustained release gene delivery system based on polymerosome-entrapped injectable hydrogel for articular cartilage tissue engineering: a hypothetical approach

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-۱ (IGF-۱) 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-۱ (IL-۱) known as a key mediator of cartilage loss in OA, and therefore, IL-۱ receptor antagonist (IL-۱Ra) gene transfer showed the therapeutic effects in experimental models of OA. Here, we argue the potential of intra-articular IGF-۱ and IL-۱Ra 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.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-۱ (IGF-۱) 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-۱ (IL-۱) known as a key mediator of cartilage loss in OA, and therefore, IL-۱ receptor antagonist (IL-۱Ra) gene transfer showed the therapeutic effects in experimental models of OA. Here, we argue the potential of intra-articular IGF-۱ and IL-۱Ra 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.

کلیدواژه ها:

Osteoarthritis ، Gene therapy ، Injectable hydrogel ، Sustained release ، Polymerosome