Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-B signal transduction pathway

abstract: ...Graphene oxide (GO) has been used as a delivery vehicle for small molecule drugs and nucleotides. To further investigate GO as a smart biomaterial for the controlled release of cargo molecules, we hypothesized that GO may be an appropriate delivery vehicle because it releases bone morphogenetic protein 2 (BMP2). GO characterization indicated that the size distribution of the GO flakes ranged from 81.1 nm to 45,749.7 nm, with an approximate thickness of 2 nm. After BMP2 adsorption onto GO, Fourier-transformed infrared spectroscopy (FTIR) and thermal gravimetric analysis were performed. Compared to GO, BMP2-GO did not induce significant changes in the characteristics of the materials. GO continuously released BMP2 for at least 40 days. Bone marrow stem cells (BMSCs) and chondrocytes were treated with BMP2-GO in interleukin-1 media and assessed in terms of cell viability, flow cytometric characterization, and expression of particular mRNA. Compared to GO, BMP2-GO did not induce any significant changes in biocompatibility. We treated osteoarthritic rats with BMP2 and BMP2-GO, which showed significant differences in Osteoarthritis Research Society International (OARSI) scores ( P <0.05). Quantitative assessment revealed significant differences compared to that using BMP2 and BMP2-GO ( P <0.05). These findings indicate that GO may be potentially used to control the release of carrier materials. The combination of BMP2 and GO slowed the progression of NF-B-activated degenerative changes in osteoarthritis. Therefore, we infer that our BMP2-GO strategy could alleviate the NF-B pathway by inducing continuous BMP2 release.

... biomaterial for the controlled release of cargo molecules, we hypothesized that GO may be an appropriate delivery vehicle because it releases bone morphogenetic protein 2 (BMP2). GO characterization indicated that the size distribution of the GO flakes ranged from 81.1 nm to 45,749.7 nm, with an approximate thickness of 2 nm. After BMP2 adsorption onto GO, Fourier-transformed infrared spectroscopy (FTIR) and thermal gravimetric analysis were performed. Compared to GO, BMP2-GO did not induce significant changes in the characteristics of the materials. GO continuously released BMP2 for at least 40 days. Bone marrow stem cells (BMSCs) and chondrocytes were treated with BMP2-GO in interleukin-1 media and assessed in terms of cell viability, flow cytometric characterization, and expression of particular mRNA. Compared to GO, BMP2-GO did not induce any significant changes in biocompatibility. We treated osteoarthritic rats with BMP2 and BMP2-GO, which showed significant differences in Osteoarthritis Research Society International (OARSI) scores ( P <0.05). Quantitative assessment revealed significant differences compared to that using BMP2 and BMP2-GO ( P <0.05). These findings indicate that GO may be potentially used to control the release of carrier materials. The combination of BMP2 and GO slowed the progression of NF-B-activated degenerative changes in osteoarthritis. Therefore, we infer that our BMP2-GO strategy could alleviate the NF-B pathway by inducing continuous BMP2 release. Keywords graphene oxide BMP2 controlled release anti-inflammatory Introduction Osteoarthritis (OA) is a degenerative joint disease that leads to the destruction of cartilage, followed by reactive hyperplasia of articular cartilage edge, and formation of osteophytes. 1 Age, obesity, strain, joint trauma, congenital abnormality, and joint deformity are risk factors for OA. 2 Treatment of more advanced stages of OA may involve artificial joint replacement, which is currently recognized as the most effective method that could significantly improve the quality of life of patients. 3 Normal bone morphogenetic protein 2 (BMP2) is an important protein component that is involved in the maintenance of the structure and function of cartilage. 4 BMP2 expression significantly increases during cartilage damage. 5 Thus, it is an important function of BMP2 to maintain the formation of articular cartilage and repair damaged cartilage. 6 Inappropriate BMP2 dosages often cause side effects and raise the costs of treatment programs after surgery. Serious complications such as immune responses, ectopic bone formation, swelling of surgical site, postoperative tissue injury, and osteolysis are caused by inappropriate administration of BMP2. 7 , 8 Therefore, it is necessary to appropriately administer BMP2 to avoid these complications. 9 The optimal administration model for BMP2 for the restoration of cartilage is dependent on its delivery vehicle. A number of delivery vehicles that release BMP2 have been evaluated, which include fibrin gels, 10 poly(lactic-co-glycolic acid) (PLGA), 11 chitosan, 12 PLGA nanospheres, 13 and hydrogels. 14 The ideal vehicle should reduce BMP2 usage for cartilage protection. Graphene oxide (GO) has been employed as an in vivo delivery vehicle for small molecule drugs and nucleotides because of its steady biocompatibility, 15 low toxicity, 16 and excellent loading capacity. 9 , 17 One essential characteristic of GO is its hydrophobic domains in the core, which are ionized along the edges

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Gene: BMP2 - bone morphogenetic protein 2 - (NCBI)

Protein : 1es7

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