Effect of ibuprofen on osteogenic properties of matrices carrying adenovirus with the BMP2 gene
Authors:   Research Centre for Medical Genetics, Moscow, Nedorubova I.A. , Chernomyrdina V.O. ,   Research Centre for Medical Genetics, Moscow,   Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Meglei A.Yu. ,   Research Centre for Medical Genetics, Moscow,   Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Basina V.P. ,   Research Centre for Medical Genetics, Moscow, Kuznetsova V.S. ,   Research Centre for Medical Genetics, Moscow,   Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Vasilyev A.V. ,   Research Centre for Medical Genetics, Moscow,   Central Research Institute of Dentistry and Maxillofacial Surgery, Moscow, Grigoriev T.E. ,   National Research Centre Kurchatov Institute, Moscow,   Moscow Institute of Physics and Technology, Moscow, Russia, Zagoskin Yu.D. ,   National Research Centre Kurchatov Institute, Moscow, Chvalun S.N. ,   National Research Centre Kurchatov Institute, Moscow, Goldshtein D.V. ,   Research Centre for Medical Genetics, Moscow, Bukharova T.B. ,   Research Centre for Medical Genetics, Moscow
Published: November 2024

Introduction. The development of gene-activated osteoplastic materials opens up new opportunities for effective treatment of patients with bone deficiency. Materials and methods. The study was carried out using multipotent mesenchymal stromal cells (MSCs) isolated from adipose tissue of rats. We obtained matrices based on polylactide acid granules (PLA granules), type I collagen, and fibrin that were impregnated with adenovirus with the BMP2 gene (Ad-BMP2) and ibuprofen. Cell adhesion on the matrices was assessed with scanning electron microscopy. The release kinetics of adenoviruses and ibuprofen was studied with spectrophotometry and UV spectrophotometry, respectively. We used real-time PCR to evaluate the efficiency of osteogenic differentiation of cells with the expression of genes of osteogenic markers; enzyme-linked immunosorbent assay to assess the production of proteins; and alizarin red staining to analyze the activity of alkaline phosphatase and the mineralization of the MSCs extracellular matrix. Results. The addition of ibuprofen during transduction of MSCs with adenoviruses with the BMP2 gene not only contributed to the effective delivery of the target gene and production of the BMP-2 protein, but also ensured more pronounced osteogenic differentiation of cells. The inclusion of ibuprofen in matrices based on PLA granules, type I collagen, and fibrin made it possible to achieve long-term release of the drug from the material. The developed matrices impregnated with Ad-BMP2 and ibuprofen are characterized by high adhesive properties. Viruses released from the matrices effectively transduced cells and induced osteogenic differentiation of MSCs. Conclusion. The developed matrices containing adenovirus with the BMP2 gene and ibuprofen have osteogenic properties in vitro and a high potential use in the treatment of bone defects. Keywords: adenoviral vectors, ibuprofen, bone morphogenetic protein, polylactide, collagen, fibrin, osteogenic differentiation