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Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels

Compositions based on chitosan/β-glycerophosphate hydrogels with highly porous polylactide granules can be used to obtain moldable bone graft materials that have osteoinductive and osteoconductive properties. To eliminate the influence of such characteristics as chain length, degree of purification,...

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Autores principales: Vasilyev, Andrey Vyacheslavovich, Kuznetsova, Valeriya Sergeevna, Bukharova, Tatyana Borisovna, Grigoriev, Timofei Evgenevich, Zagoskin, Yuriy Dmitrievich, Nedorubova, Irina Alekseevna, Babichenko, Igor Ivanovich, Chvalun, Sergey Nicolaevich, Goldstein, Dmitry Vadimovich, Kulakov, Anatoliy Alekseevich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825646/
https://www.ncbi.nlm.nih.gov/pubmed/33430198
http://dx.doi.org/10.3390/molecules26020261
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author Vasilyev, Andrey Vyacheslavovich
Kuznetsova, Valeriya Sergeevna
Bukharova, Tatyana Borisovna
Grigoriev, Timofei Evgenevich
Zagoskin, Yuriy Dmitrievich
Nedorubova, Irina Alekseevna
Babichenko, Igor Ivanovich
Chvalun, Sergey Nicolaevich
Goldstein, Dmitry Vadimovich
Kulakov, Anatoliy Alekseevich
author_facet Vasilyev, Andrey Vyacheslavovich
Kuznetsova, Valeriya Sergeevna
Bukharova, Tatyana Borisovna
Grigoriev, Timofei Evgenevich
Zagoskin, Yuriy Dmitrievich
Nedorubova, Irina Alekseevna
Babichenko, Igor Ivanovich
Chvalun, Sergey Nicolaevich
Goldstein, Dmitry Vadimovich
Kulakov, Anatoliy Alekseevich
author_sort Vasilyev, Andrey Vyacheslavovich
collection PubMed
description Compositions based on chitosan/β-glycerophosphate hydrogels with highly porous polylactide granules can be used to obtain moldable bone graft materials that have osteoinductive and osteoconductive properties. To eliminate the influence of such characteristics as chain length, degree of purification, and molecular weight on a designed material, the one-stock chitosan sample was reacetylated to degrees of deacetylation (DD%) of 19.5, 39, 49, 55, and 56. A study of the chitosan/β-glycerophosphate hydrogel with chitosan of a reduced DD% showed that a low degree of deacetylation increased the MSCs (multipotent stromal cells) viability rate in vitro and reduced the leukocyte infiltration in subcutaneous implantation to Wistar rats in vivo. The addition of 12 wt% polylactide granules resulted in optimal composite mechanical and moldable properties, and increased the modulus of elasticity of the hydrogel-based material by approximately 100 times. Excessive filling of the material with PLA (polylactide) granules (more than 20%) led to material destruction at a ~10% strain. Osteoinductive and osteoconductive properties of the chitosan hydrogel-based material with reacetylated chitosan (39 DD%) and highly porous polylactide granules impregnated with BMP-2 (bone morphogenetic protein-2) have been demonstrated in models of orthotopic and ectopic bone formation. When implanted into a critical-size calvarial defect in rats, the optimal concentration of BMP-2 was 10 μg/mL: bone tissue areas filled the entire material’s thickness. Implantation of the material with 50 μg/mL BMP-2 was accompanied with excessive growth of bone tissue and material displacement beyond the defect. Significant osteoinductive and osteoconductive properties of the material with 10 μg/mL of BMP-2 were also shown in subcutaneous implantation.
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spelling pubmed-78256462021-01-24 Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels Vasilyev, Andrey Vyacheslavovich Kuznetsova, Valeriya Sergeevna Bukharova, Tatyana Borisovna Grigoriev, Timofei Evgenevich Zagoskin, Yuriy Dmitrievich Nedorubova, Irina Alekseevna Babichenko, Igor Ivanovich Chvalun, Sergey Nicolaevich Goldstein, Dmitry Vadimovich Kulakov, Anatoliy Alekseevich Molecules Article Compositions based on chitosan/β-glycerophosphate hydrogels with highly porous polylactide granules can be used to obtain moldable bone graft materials that have osteoinductive and osteoconductive properties. To eliminate the influence of such characteristics as chain length, degree of purification, and molecular weight on a designed material, the one-stock chitosan sample was reacetylated to degrees of deacetylation (DD%) of 19.5, 39, 49, 55, and 56. A study of the chitosan/β-glycerophosphate hydrogel with chitosan of a reduced DD% showed that a low degree of deacetylation increased the MSCs (multipotent stromal cells) viability rate in vitro and reduced the leukocyte infiltration in subcutaneous implantation to Wistar rats in vivo. The addition of 12 wt% polylactide granules resulted in optimal composite mechanical and moldable properties, and increased the modulus of elasticity of the hydrogel-based material by approximately 100 times. Excessive filling of the material with PLA (polylactide) granules (more than 20%) led to material destruction at a ~10% strain. Osteoinductive and osteoconductive properties of the chitosan hydrogel-based material with reacetylated chitosan (39 DD%) and highly porous polylactide granules impregnated with BMP-2 (bone morphogenetic protein-2) have been demonstrated in models of orthotopic and ectopic bone formation. When implanted into a critical-size calvarial defect in rats, the optimal concentration of BMP-2 was 10 μg/mL: bone tissue areas filled the entire material’s thickness. Implantation of the material with 50 μg/mL BMP-2 was accompanied with excessive growth of bone tissue and material displacement beyond the defect. Significant osteoinductive and osteoconductive properties of the material with 10 μg/mL of BMP-2 were also shown in subcutaneous implantation. MDPI 2021-01-07 /pmc/articles/PMC7825646/ /pubmed/33430198 http://dx.doi.org/10.3390/molecules26020261 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vasilyev, Andrey Vyacheslavovich
Kuznetsova, Valeriya Sergeevna
Bukharova, Tatyana Borisovna
Grigoriev, Timofei Evgenevich
Zagoskin, Yuriy Dmitrievich
Nedorubova, Irina Alekseevna
Babichenko, Igor Ivanovich
Chvalun, Sergey Nicolaevich
Goldstein, Dmitry Vadimovich
Kulakov, Anatoliy Alekseevich
Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels
title Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels
title_full Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels
title_fullStr Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels
title_full_unstemmed Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels
title_short Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels
title_sort influence of the degree of deacetylation of chitosan and bmp-2 concentration on biocompatibility and osteogenic properties of bmp-2/pla granule-loaded chitosan/β-glycerophosphate hydrogels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825646/
https://www.ncbi.nlm.nih.gov/pubmed/33430198
http://dx.doi.org/10.3390/molecules26020261
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