Hybrid Implants Based on Calcium-Magnesium Silicate Ceramics Diopside as a Carrier of Recombinant BMP-2 and Demineralized Bone Matrix as a Scaffold: Dynamics of Reparative Osteogenesis in a Mouse Craniotomy Model

Karyagina, A. S.; Orlova, Polina; Poponova, M. S.; Bulygina, Inna; Choudhary, Rajan; Zhulina, A.V.; Грунина, Т. М.; Nikitin, Kirill; Strukova, Natalia; Generalova, Maria; Ryazanova, Anna V; Kovaleva, Polina A.; Zimina, Anna; Lukinova, Ekaterina; Plakhotniuk, Egor; Kirsanova, Mariya; Kolesnikov, Evgeniy; Захарова, Елена; Манских, В. Н.; Сенатов, Ф.С.; Gromov, A. V.

doi:10.1134/s0006297922110074

Cited by 6 publications

(6 citation statements)

References 47 publications

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“…The amount of lysostaphin adsorbed to and released from the diopside powder was high enough to fully eliminate planktonic cells and eradicate biofilms of S. aureus . However, lysostaphin adsorbed less efficiently than previously reported recombinant BMP-2, with more than 150 μg of BMP-2 adsorbed per 1 mg of diopside [ 28 ] compared to only 5.20 μg of lysostaphin. This difference could be attributed to the differences in the general physicochemical properties of these proteins, such as solubility and isoelectric point.…”

Section: Discussionmentioning

confidence: 72%

“…To further improve the properties and extend the range of applications of an implanted material, it is desirable to be able to functionalize it with additional active molecules such as various recombinant proteins. We have previously demonstrated that the loading of diopside-based material with recombinant BMP-2 enhances its osteoinductive properties [ 28 ]. In this work, we have addressed the possibility of loading diopside powder with antibacterial protein to lower the risks of implant-associated infections.…”

Section: Discussionmentioning

confidence: 99%

“…Diopside (CaMgSi 2 O 6 ) was synthesized by a ball-milling-assisted solid-state method as described earlier [ 28 ]. Briefly, an appropriate amount of powdered eggshells, synthetic magnesium oxide, and silica extracted from rice husk were mixed by using ball milling to reduce particle size as well as generate homogeneity.…”

Section: Methodsmentioning

confidence: 99%

“…These properties make diopside potentially promising as a replacement for calcium-phosphate ceramics such as HA for use as a protein carrier in implants. Recently, the adsorption capacity of diopside toward recombinant BMP-2 [ 27 ] has been shown to be three times greater than that of nano-HA [ 28 ]. Implants with diopside impregnated with BMP-2 demonstrated high osteoinductivity in vivo [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, the adsorption capacity of diopside toward recombinant BMP-2 [ 27 ] has been shown to be three times greater than that of nano-HA [ 28 ]. Implants with diopside impregnated with BMP-2 demonstrated high osteoinductivity in vivo [ 28 ]. This suggests that diopside may be an effective carrier for other proteins as well.…”

Section: Introductionmentioning

confidence: 99%

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Antibacterial and Anti-Biofilm Properties of Diopside Powder Loaded with Lysostaphin

et al. 2023

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Background: Diopside-based ceramic is a perspective biocompatible material with numerous potential applications in the field of bone prosthetics. Implantable devices and materials are often prone to colonization and biofilm formation by pathogens such as Staphylococcus aureus, which in the case of bone grafting leads to osteomyelitis, an infectious bone and bone marrow injury. To lower the risk of bacterial colonization, implanted materials can be impregnated with antimicrobials. In this work, we loaded the antibacterial enzyme lysostaphin on diopside powder and studied the antibacterial and antibiofilm properties of such material to probe the utility of this approach for diopside-based prosthetic materials. Methods: Diopside powder was synthesized by the solid-state method, lysostaphin was loaded on diopside by adsorption, the release of lysostaphin from diopside was monitored by ELISA, and antibacterial and anti-biofilm activity was assessed by standard microbiological procedures. Results and conclusions: Lysostaphin released from diopside powder showed high antibacterial activity against planktonic bacteria and effectively destroyed 24-h staphylococcal biofilms. Diopside-based materials possess a potential for the development of antibacterial bone grafting materials.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antibacterial and Anti-Biofilm Properties of Diopside Powder Loaded with Lysostaphin

et al. 2023

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Dual‐Functional Implant Based on Gellan‐Xanthan Hydrogel with Diopside, BMP‐2 and Lysostaphin for Bone Defect Repair and Control of Staphylococcal Infection

Karyagina,

Grishin,

Kudinova

et al. 2024

Macromolecular Bioscience

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A new dual‐functional implant based on gellan‐xanthan hydrogel with calcium‐magnesium silicate ceramic diopside and recombinant lysostaphin and bone morphogenetic protein 2 (BMP‐2)‐ray is developed. In this composite, BMP‐2 is immobilized on microparticles of diopside while lysostaphin is mixed directly into the hydrogel, providing sustained release of BMP‐2 to allow gradual bone formation and rapid release of lysostaphin to eliminate infection immediately after implantation. Introduction of diopside of up to 3% (w/v) has a negligible effect on the mechanical properties of the hydrogel but provides a high sorption capacity for BMP‐2. The hydrogels show good biocompatibility and antibacterial activity. Lysostaphin released from the implants over a 3 h period efficiently kills planktonic cells and completely destroys 24 h pre‐formed biofilms of Staphylococcus aureus. Furthermore, in vivo experiments in a mouse model of critically‐sized cranial defects infected with S. aureus show a complete lack of osteogenesis when implants contain only BMP‐2, whereas, in the presence of lysostaphin, complete closure of the defect with newly formed mineralized bone tissue is observed. Thus, the new implantable gellan‐xanthan hydrogel with diopside and recombinant lysostaphin and BMP‐2 shows both osteogenic and antibacterial properties and represents a promising material for the treatment and/or prevention of osteomyelitis after bone trauma.

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Hybrid Implants Based on Calcium-Magnesium Silicate Ceramic Diopside as a Carrier of Recombinant BMP-2 and Demineralized Bone Matrix as a Scaffold: Ectopic Osteogenesis in Intramuscular Implantation in Mice

Karyagina,

Orlova,

Zhulina

et al. 2023

Biochemistry Moscow

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High efficiency of hybrid implants based on calcium-magnesium silicate ceramic, diopside, as a carrier of recombinant BMP-2 and xenogenic demineralized bone matrix (DBM) as a scaffold for bone tissue regeneration was demonstrated previously using the model of critical size cranial defects in mice. In order to investigate the possibility of using these implants for growing autologous bone tissue using in vivo bioreactor principle in the patient’s own body, effectiveness of ectopic osteogenesis induced by them in intramuscular implantation in mice was studied. At the dose of 7 μg of BMP-2 per implant, dense agglomeration of cells, probably skeletal muscle satellite precursor cells, was observed one week after implantation with areas of intense chondrogenesis, initial stage of indirect osteogenesis, around the implants. After 12 weeks, a dense bone capsule of trabecular structure was formed covered with periosteum and mature bone marrow located in the spaces between the trabeculae. The capsule volume was about 8-10 times the volume of the original implant. There were practically no signs of inflammation and foreign body reaction. Microcomputed tomography data showed significant increase of the relative bone volume, number of trabeculae, and bone tissue density in the group of mice with BMP-2-containing implant in comparison with the group without BMP-2. Considering that DBM can be obtained in practically unlimited quantities with required size and shape, and that BMP-2 is obtained by synthesis in E. coli cells and is relatively inexpensive, further development of the in vivo bioreactor model based on the hybrid implants constructed from BMP-2, diopside, and xenogenic DBM seems promising.

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Hybrid Implants Based on Calcium-Magnesium Silicate Ceramics Diopside as a Carrier of Recombinant BMP-2 and Demineralized Bone Matrix as a Scaffold: Dynamics of Reparative Osteogenesis in a Mouse Craniotomy Model

Cited by 6 publications

References 47 publications

Antibacterial and Anti-Biofilm Properties of Diopside Powder Loaded with Lysostaphin

Antibacterial and Anti-Biofilm Properties of Diopside Powder Loaded with Lysostaphin

Dual‐Functional Implant Based on Gellan‐Xanthan Hydrogel with Diopside, BMP‐2 and Lysostaphin for Bone Defect Repair and Control of Staphylococcal Infection

Hybrid Implants Based on Calcium-Magnesium Silicate Ceramic Diopside as a Carrier of Recombinant BMP-2 and Demineralized Bone Matrix as a Scaffold: Ectopic Osteogenesis in Intramuscular Implantation in Mice

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