Recombinant Human Bone Growth Factor BMP-2 Synthesized in Escherichia coli Cells. Part 2: From Combined Use with Other P

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Recombinant Human Bone Growth Factor BMP-2 Synthesized in Escherichia coli Cells. Part 2: From Combined Use with Other Protein Factors in Animal Models to Application in Medicine A. V. Gromova, *, M. S. Poponovaa, and A. S. Karyaginaa, b, c aGamaleya National Research Center of Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation, Moscow, 123098 Russia b All-Russian Research Institute of Agricultural Biotechnology, Moscow, 127550 Russia cBelozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119234 Russia *e-mail: [email protected]

Received June 4, 2019; revised September 4, 2019; accepted September 15, 2019

Abstract—This review is devoted to current approaches to the combined use of BMP-2 with other protein factors to increase osteoinductivity of recently developed materials. The current trend is to create materials with a low BMP-2 concentration that are efficient in osteoinduction and provide continuous protein release. A number of medications have been developed in Russia and South Korea on the basis of BMP-2 synthesized in E. coli cells. The first experience of their use in orthopedics, traumatology, spinal surgery, and dental implantology showed promising results. Also, the possibility of the recombinant BMP-2 use in ophthalmology, and oncology, as well as osteoarthritis treatment, was studied. The databases of PubMed Central (U.S. National Institutes of Health’s National Library of Medicine (NIH/NLM)), PubMed (NLM National Center for Biotechnology Information (NCBI)), and e-library (Science Electronic Library) were used to analyze published results. Keywords: BMP-2, Escherichia coli, bone tissue regeneration, osteoplastic materials, review DOI: 10.3103/S0891416820020056

The first part of this review, which was published previously, contained our knowledge on the basic BMP-2 properties, mechanisms, and production of the active factor in bacteria. Also, the first part was dedicated to the BMP-2 carriers and animal models used to study the efficacy of BMP-2-based materials. This second part is dedicated to the BMP-2 use together with other factors combined in the same material, as well as to the application of these materials in medicine.

expected that the combined use of biologically active factors will lead to more successful results in bone tissue regeneration because there exist many growth factors and cytokines involved in these processes. The variety of factors used with BMP-2 that affect bone tissue regeneration include erythropoietin (erythropoietin, EPO) [1–3], stromal cell-derived factor 1 (SDF-1) [4–8], vascular endothelial growth factor (VEGF) [9–12], platelet-derived growth factor (PDGF) [12, 13], insulin-like growth factor-1 (IGF-1) [14], and fibroblast growth factor 2 (FGF-2) [15, 16]. In this review, we focused on studies that included bacterial BMP-2 and, sometimes, BMP-2 of unknown origin (see Table 1).

APPLICATION OF BMP-2 COMBINED WITH OTHER FACTORS The use of BMP-2 of bacterial origin combined with other biologically