Two variants of recombinant human bone morphogenetic protein-2 (rhBMP-2) with additional protein domains: Synthesis in an Escherichia coli heterologous expression system

Karyagina, A. S.; Boksha, Irina S.; Грунина, Т. М.; Демиденко, А. В.; Poponova, M. S.; Сергиенко, О. В.; Lyashchuk, A. M.; Галушкина, З. М.; Soboleva, L. A.; Osidak, E. O.; Бартов, М. С.; Gromov, A. V.; Лунин, В. Г.

doi:10.1134/s0006297917050091

Cited by 21 publications

(5 citation statements)

References 25 publications

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“…BMP-2 was synthesized in an Escherichia coli heterologous expression system and purified using metal-chelating chromatography on WorkBeads 40 Ni and affinity chromatography on heparin-sepharose . The biological activity of BMP-2 was confirmed and determined as the activity of alkaline phosphatase produced by C2C12 myoblasts after the addition of BMP-2 in culture medium .…”

Section: Methodsmentioning

confidence: 99%

Development of Optimized Strategies for Growth Factor Incorporation onto Electrospun Fibrous Scaffolds To Promote Prolonged Release

Karpov

Peltek

Muslimov

et al. 2019

ACS Appl. Mater. Interfaces

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Growth factor incorporation in biomedical constructs for their local delivery enables specific pharmacological effects such as the induction of cell growth and differentiation. This has enabled a promising way to improve the tissue regeneration process. However, it remains challenging to identify an appropriate approach that provides effective growth factor loading into biomedical constructs with their following release kinetics in a prolonged manner. In the present work, we performed a systematic study, which explores the optimal strategy of growth factor incorporation into sub-micrometric-sized CaCO3 core–shell particles (CSPs) and hollow silica particles (SiPs). These carriers were immobilized onto the surface of the polymer scaffolds based on polyhydroxybutyrate (PHB) with and without reduced graphene oxide (rGO) in its structure to examine the functionality of incorporated growth factors. Bone morphogenetic protein-2 (BMP-2) and ErythroPOietin (EPO) as growth factor models were included into CSPs and SiPs using different entrapping strategies, namely, physical adsorption, coprecipitation technique, and freezing-induced loading method. It was shown that the loading efficiency, release characteristics, and bioactivity of incorporated growth factors strongly depend on the chosen strategy of their incorporation into delivery systems. Overall, we demonstrated that the combination of scaffolds with drug delivery systems containing growth factors has great potential in the field of tissue regeneration compared with individual scaffolds.

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Section: Methodsmentioning

confidence: 99%

Development of Optimized Strategies for Growth Factor Incorporation onto Electrospun Fibrous Scaffolds To Promote Prolonged Release

Karpov

Peltek

Muslimov

et al. 2019

ACS Appl. Mater. Interfaces

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“…The BE of XPS Cu2p 3/2 spectrum is 932.6 eV (Figure 4e). Since the BE values of metallic Cu and Cu 2 O are very similar, 932.6 and 932.4 eV, respectively, 50 Auger parameter can be used to distinguish Cu(0) and Cu(I) states. The Auger spectrum of the PEO-Cu coating is depicted in Figure 4f.…”

Section: Resultsmentioning

confidence: 99%

Osteoconductive, Osteogenic, and Antipathogenic Plasma Electrolytic Oxidation Coatings on Titanium Implants with BMP-2

Popova,

Sheveyko,

Kuptsov

et al. 2023

ACS Appl. Mater. Interfaces

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We report a one-pot plasma electrolytic oxidation (PEO) strategy for forming a multi-element oxide layer on the titanium surface using complex electrolytes containing Na 2 HPO 4 , Ca(OH) 2 , (NH 2 ) 2 CO, Na 2 SiO 3 , CuSO 4 , and KOH compounds. For even better bone implant ingrowth, PEO coatings were additionally loaded with bone morphogenetic protein-2 (BMP-2). The samples were tested in vivo in a mouse craniotomy model. Tests for bactericidal and fungicidal activity were carried out using clinically isolated multi-drug-resistant Escherichia coli (E. coli) K261, E. coli U20, methicillin-resistant Staphylococcus aureus (S. aureus) CSA154 bacterial strains, and Neurospora crassa (N. crassa) and Candida albicans (C. albicans) D2528/20 fungi. The PEO-Cu coating effectively inactivated both Gram-positive and Gram-negative bacteria at low concentrations of Cu 2+ ions: minimal bactericidal concentration for E. coli and N. crassa (99.9999%) and minimal inhibitory concentration (99.0%) for S. aureus were 5 ppm. For all studied bacterial and fungal strains, PEO-Cu coating completely prevented the formation of bacterial and fungal biofilms. PEO and PEO-Cu coatings demonstrated bone remodeling and moderate osteoconductivity in vivo, while BMP-2 significantly enhanced osteoconduction and osteogenesis. The obtained results are encouraging and indicate that Ti-based materials with PEO coatings loaded with BMP-2 can be widely used in customized medicine as implants for orthopedics and craniomaxillofacial surgery.

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“…The extraction and purification of small quantities of BMPs began from demineralized cadaveric bovine bone sources, a technique that required a very long production time and a contribution of several kilograms of bone at a very high cost (several kg of bone = µg of purified BMPs) [ 375 ]. Subsequently, this procedure was replaced by the molecular cloning of coding sequences (cDNA) for members of the BMPs family expressed in different recombinant systems (Bacteria: Escherichia coli ; Yeast based: Pichia pastoris; Baculovirus/insect cell system (Baculovirus Expression Vector Systems: BEVS); and Mammalian cells: Chinese hamster ovary (CHO)) [ 137 , 376 , 377 , 378 ]. This strategy made it possible to obtain a higher yield of proteins and a better reproducibility, reliability, and safety of the BMPs produced.…”

Section: The Use Of Members Of the Tgf-β Superfamily In Clinical Amentioning

confidence: 99%

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions

Jann

Gascon

Roux

et al. 2020

IJMS

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The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors—in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins—not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of osteoclastogenesis, osteogenic differentiation of stem cells, and osteoblasts/osteoclasts balance. After introducing the main types of bone cells, their differentiation and cooperation during bone remodeling and fracture healing processes are discussed. Then, the TGF-β superfamily, its signaling via canonical and non-canonical pathways, as well as its regulation by Wnt/Notch or microRNAs are described and discussed. Its important role in bone homeostasis, repair, or disease is also highlighted. Finally, the clinical therapeutic uses of members of the TGF-β superfamily and their associated complications are debated.

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Two variants of recombinant human bone morphogenetic protein-2 (rhBMP-2) with additional protein domains: Synthesis in an Escherichia coli heterologous expression system

Cited by 21 publications

References 25 publications

Development of Optimized Strategies for Growth Factor Incorporation onto Electrospun Fibrous Scaffolds To Promote Prolonged Release

Development of Optimized Strategies for Growth Factor Incorporation onto Electrospun Fibrous Scaffolds To Promote Prolonged Release

Osteoconductive, Osteogenic, and Antipathogenic Plasma Electrolytic Oxidation Coatings on Titanium Implants with BMP-2

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions

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