Osteoinductive Moldable and Curable Bone Substitutes Based on Collagen, BMP-2 and Highly Porous Polylactide Granules, or a Mix of HAP/β-TCP

Vasilyev, Andrey Vyacheslavovich; Kuznetsova, Valeriya Sergeevna; Bukharova, Tatyana Borisovna; Osidak, Egor Olegovich; Grigoriev, Timofei Evgenevich; Zagoskin, Yuriy Dmitrievich; Nedorubova, Irina Alekseevna; Domogatsky, Sergey Petrovich; Babichenko, Igor Ivanovich; Zorina, Oksana Aleksandrovna; Kutsev, Sergey Ivanovich; Chvalun, Sergei Nicolaevich; Kulakov, Anatoly Alekseevich; Losev, Fedor Fedorovich; Goldshtein, Dmitry Vadimovich

doi:10.3390/polym13223974

Open AccessArticle

Osteoinductive Moldable and Curable Bone Substitutes Based on Collagen, BMP-2 and Highly Porous Polylactide Granules, or a Mix of HAP/β-TCP

by

Andrey Vyacheslavovich Vasilyev

^1,2,6,7,*

,

Valeriya Sergeevna Kuznetsova

^1,2

,

Tatyana Borisovna Bukharova

¹

,

Egor Olegovich Osidak

³

,

Timofei Evgenevich Grigoriev

^5,8,

Yuriy Dmitrievich Zagoskin

⁵,

Irina Alekseevna Nedorubova

¹

,

Sergey Petrovich Domogatsky

^3,4,

Igor Ivanovich Babichenko

^2,6,

Oksana Aleksandrovna Zorina

^2,7,

Sergey Ivanovich Kutsev

¹,

Sergei Nicolaevich Chvalun

⁵,

Anatoly Alekseevich Kulakov

²,

Fedor Fedorovich Losev

^2,7 and

Dmitry Vadimovich Goldshtein

¹

Research Centre for Medical Genetics, Moskvorechye st., 1, 115478 Moscow, Russia

²

Central Research Institute of Dental and Maxillofacial Surgery, Timur Frunze st., 16, 119021 Moscow, Russia

³

Imtek Ltd., 3rd Cherepkovskaya st., 15a, 121552 Moscow, Russia

⁴

Federal State Budgetary Institution National Medical Research Center of Cardiology Ministry of Health of the Russian Federation, 3rd Cherepkovskaya st., 15a, 121552 Moscow, Russia

⁵

NRC “Kurchatov Institute”, 1, Akademika Kurchatova pl, 123182 Moscow, Russia

⁶

Department of Pathological Anatomy, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya st., 117198 Moscow, Russia

⁷

I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia

⁸

Moscow Institute of Physics and Technology (National Research University), 9 Institutskiy per., Dolgoprudny, 141701 Moscow, Russia

^*

Author to whom correspondence should be addressed.

Polymers 2021, 13(22), 3974; https://doi.org/10.3390/polym13223974

Submission received: 19 October 2021 / Revised: 11 November 2021 / Accepted: 12 November 2021 / Published: 17 November 2021

(This article belongs to the Special Issue New Composites for Medical Applications)

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Abstract

In dentistry, maxillofacial surgery, traumatology, and orthopedics, there is a need to use osteoplastic materials that have not only osteoinductive and osteoconductive properties but are also convenient for use. In the study, compositions based on collagen hydrogel were developed. Polylactide granules (PLA) or a traditional bone graft, a mixture of hydroxyapatite and β-tricalcium phosphate (HAP/β-TCP), were used for gel filling to improve mechanical osteoconductive properties of compositions. The mechanical tests showed that collagen hydrogels filled with 12 wt% highly porous PLA granules (elastic modulus 373 ± 55 kPa) or 35 wt% HAP/β-TCP granules (elastic modulus 451 ± 32 kPa) had optimal manipulative properties. All composite components were cytocompatible. The cell’s viability was above 90%, and the components’ structure facilitated the cell’s surface adhesion. The bone morphogenetic protein-2 (BMP-2) provided osteoinductive composition properties. It was impregnated directly into the collagen hydrogel with the addition of fibronectin or inside porous PLA granules. The implantation of a collagen hydrogel with BMP-2 and PLA granules into a critical-size calvarial defect in rats led to the formation of the most significant volume of bone tissue: 61 ± 15%. It was almost 2.5 times more than in the groups where a collagen-fibronectin hydrogel with a mixture of HAP/β-TCP (25 ± 7%) or a fibronectin-free composition with porous PLA granules impregnated with BMP-2 (23 ± 8%) were used. Subcutaneous implantation of the compositions also showed their high biocompatibility and osteogenic potential in the absence of a bone environment. Thus, the collagen-fibronectin hydrogel with BMP-2 and PLA granules has optimal biocompatibility, osteogenic, and manipulative properties.

Keywords: collagen; fibronectin; hydrogel; polylactide; HAP/β-TCP; BMP-2; osteoinduction

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MDPI and ACS Style

Vasilyev, A.V.; Kuznetsova, V.S.; Bukharova, T.B.; Osidak, E.O.; Grigoriev, T.E.; Zagoskin, Y.D.; Nedorubova, I.A.; Domogatsky, S.P.; Babichenko, I.I.; Zorina, O.A.; et al. Osteoinductive Moldable and Curable Bone Substitutes Based on Collagen, BMP-2 and Highly Porous Polylactide Granules, or a Mix of HAP/β-TCP. Polymers 2021, 13, 3974. https://doi.org/10.3390/polym13223974

AMA Style

Vasilyev AV, Kuznetsova VS, Bukharova TB, Osidak EO, Grigoriev TE, Zagoskin YD, Nedorubova IA, Domogatsky SP, Babichenko II, Zorina OA, et al. Osteoinductive Moldable and Curable Bone Substitutes Based on Collagen, BMP-2 and Highly Porous Polylactide Granules, or a Mix of HAP/β-TCP. Polymers. 2021; 13(22):3974. https://doi.org/10.3390/polym13223974

Chicago/Turabian Style

Vasilyev, Andrey Vyacheslavovich, Valeriya Sergeevna Kuznetsova, Tatyana Borisovna Bukharova, Egor Olegovich Osidak, Timofei Evgenevich Grigoriev, Yuriy Dmitrievich Zagoskin, Irina Alekseevna Nedorubova, Sergey Petrovich Domogatsky, Igor Ivanovich Babichenko, Oksana Aleksandrovna Zorina, and et al. 2021. "Osteoinductive Moldable and Curable Bone Substitutes Based on Collagen, BMP-2 and Highly Porous Polylactide Granules, or a Mix of HAP/β-TCP" Polymers 13, no. 22: 3974. https://doi.org/10.3390/polym13223974

APA Style

Vasilyev, A. V., Kuznetsova, V. S., Bukharova, T. B., Osidak, E. O., Grigoriev, T. E., Zagoskin, Y. D., Nedorubova, I. A., Domogatsky, S. P., Babichenko, I. I., Zorina, O. A., Kutsev, S. I., Chvalun, S. N., Kulakov, A. A., Losev, F. F., & Goldshtein, D. V. (2021). Osteoinductive Moldable and Curable Bone Substitutes Based on Collagen, BMP-2 and Highly Porous Polylactide Granules, or a Mix of HAP/β-TCP. Polymers, 13(22), 3974. https://doi.org/10.3390/polym13223974

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Osteoinductive Moldable and Curable Bone Substitutes Based on Collagen, BMP-2 and Highly Porous Polylactide Granules, or a Mix of HAP/β-TCP

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