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,...

Full description

Bibliographic Details
Main Authors: Andrey Vyacheslavovich Vasilyev, Valeriya Sergeevna Kuznetsova, Tatyana Borisovna Bukharova, Timofei Evgenevich Grigoriev, Yuriy Dmitrievich Zagoskin, Irina Alekseevna Nedorubova, Igor Ivanovich Babichenko, Sergey Nicolaevich Chvalun, Dmitry Vadimovich Goldstein, Anatoliy Alekseevich Kulakov
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/2/261
_version_ 1797415606229663744
author Andrey Vyacheslavovich Vasilyev
Valeriya Sergeevna Kuznetsova
Tatyana Borisovna Bukharova
Timofei Evgenevich Grigoriev
Yuriy Dmitrievich Zagoskin
Irina Alekseevna Nedorubova
Igor Ivanovich Babichenko
Sergey Nicolaevich Chvalun
Dmitry Vadimovich Goldstein
Anatoliy Alekseevich Kulakov
author_facet Andrey Vyacheslavovich Vasilyev
Valeriya Sergeevna Kuznetsova
Tatyana Borisovna Bukharova
Timofei Evgenevich Grigoriev
Yuriy Dmitrievich Zagoskin
Irina Alekseevna Nedorubova
Igor Ivanovich Babichenko
Sergey Nicolaevich Chvalun
Dmitry Vadimovich Goldstein
Anatoliy Alekseevich Kulakov
author_sort Andrey Vyacheslavovich Vasilyev
collection DOAJ
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.
first_indexed 2024-03-09T05:51:05Z
format Article
id doaj.art-324eb3ddbd4a45f8867673974efe4a36
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-09T05:51:05Z
publishDate 2021-01-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-324eb3ddbd4a45f8867673974efe4a362023-12-03T12:17:21ZengMDPI AGMolecules1420-30492021-01-0126226110.3390/molecules26020261Influence 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 HydrogelsAndrey Vyacheslavovich Vasilyev0Valeriya Sergeevna Kuznetsova1Tatyana Borisovna Bukharova2Timofei Evgenevich Grigoriev3Yuriy Dmitrievich Zagoskin4Irina Alekseevna Nedorubova5Igor Ivanovich Babichenko6Sergey Nicolaevich Chvalun7Dmitry Vadimovich Goldstein8Anatoliy Alekseevich Kulakov9Research Centre for Medical Genetics, Moskvorechye st., 1, 115478 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechye st., 1, 115478 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechye st., 1, 115478 Moscow, RussiaNRC “Kurchatov Institute”, 1, Akademika Kurchatova pl., 123182 Moscow, RussiaNRC “Kurchatov Institute”, 1, Akademika Kurchatova pl., 123182 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechye st., 1, 115478 Moscow, RussiaCentral Research Institute of Dental and Maxillofacial Surgery, Timur Frunze st., 16, 119021 Moscow, RussiaNRC “Kurchatov Institute”, 1, Akademika Kurchatova pl., 123182 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechye st., 1, 115478 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechye st., 1, 115478 Moscow, RussiaCompositions 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.https://www.mdpi.com/1420-3049/26/2/261chitosandeacetylation degreeosteoplastic materialBMP-2porous polylactide granulesosteoinduction
spellingShingle Andrey Vyacheslavovich Vasilyev
Valeriya Sergeevna Kuznetsova
Tatyana Borisovna Bukharova
Timofei Evgenevich Grigoriev
Yuriy Dmitrievich Zagoskin
Irina Alekseevna Nedorubova
Igor Ivanovich Babichenko
Sergey Nicolaevich Chvalun
Dmitry Vadimovich Goldstein
Anatoliy Alekseevich Kulakov
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
Molecules
chitosan
deacetylation degree
osteoplastic material
BMP-2
porous polylactide granules
osteoinduction
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 chitosan
deacetylation degree
osteoplastic material
BMP-2
porous polylactide granules
osteoinduction
url https://www.mdpi.com/1420-3049/26/2/261
work_keys_str_mv AT andreyvyacheslavovichvasilyev influenceofthedegreeofdeacetylationofchitosanandbmp2concentrationonbiocompatibilityandosteogenicpropertiesofbmp2plagranuleloadedchitosanbglycerophosphatehydrogels
AT valeriyasergeevnakuznetsova influenceofthedegreeofdeacetylationofchitosanandbmp2concentrationonbiocompatibilityandosteogenicpropertiesofbmp2plagranuleloadedchitosanbglycerophosphatehydrogels
AT tatyanaborisovnabukharova influenceofthedegreeofdeacetylationofchitosanandbmp2concentrationonbiocompatibilityandosteogenicpropertiesofbmp2plagranuleloadedchitosanbglycerophosphatehydrogels
AT timofeievgenevichgrigoriev influenceofthedegreeofdeacetylationofchitosanandbmp2concentrationonbiocompatibilityandosteogenicpropertiesofbmp2plagranuleloadedchitosanbglycerophosphatehydrogels
AT yuriydmitrievichzagoskin influenceofthedegreeofdeacetylationofchitosanandbmp2concentrationonbiocompatibilityandosteogenicpropertiesofbmp2plagranuleloadedchitosanbglycerophosphatehydrogels
AT irinaalekseevnanedorubova influenceofthedegreeofdeacetylationofchitosanandbmp2concentrationonbiocompatibilityandosteogenicpropertiesofbmp2plagranuleloadedchitosanbglycerophosphatehydrogels
AT igorivanovichbabichenko influenceofthedegreeofdeacetylationofchitosanandbmp2concentrationonbiocompatibilityandosteogenicpropertiesofbmp2plagranuleloadedchitosanbglycerophosphatehydrogels
AT sergeynicolaevichchvalun influenceofthedegreeofdeacetylationofchitosanandbmp2concentrationonbiocompatibilityandosteogenicpropertiesofbmp2plagranuleloadedchitosanbglycerophosphatehydrogels
AT dmitryvadimovichgoldstein influenceofthedegreeofdeacetylationofchitosanandbmp2concentrationonbiocompatibilityandosteogenicpropertiesofbmp2plagranuleloadedchitosanbglycerophosphatehydrogels
AT anatoliyalekseevichkulakov influenceofthedegreeofdeacetylationofchitosanandbmp2concentrationonbiocompatibilityandosteogenicpropertiesofbmp2plagranuleloadedchitosanbglycerophosphatehydrogels