title: Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-κB 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-κB-activated degenerative changes in osteoarthritis. Therefore, we infer that our BMP2-GO strategy could alleviate the NF-κB pathway by inducing continuous BMP2 release.
authors.affiliation: Department of Orthopaedic, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Orthopaedic, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Xiangjin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Plastic and Reconstructive Surgery, Second Affiliated Hospital, School of Medicine; Institute of Gastroenterology, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Bao
mesh_terms: D000327:Adsorption; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006108:Graphite / Q000737:chemistry*; D007150:Immunohistochemistry; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D010003:Osteoarthritis / Q000188:drug therapy / Q000473:pathology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D055396:Bone Morphogenetic Protein 2; D016328:NF-kappa B; D006108:Graphite
keywords: BMP2; anti-inflammatory; controlled release; graphene oxide