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,...
Main Authors: | , , , , , , , , , |
---|---|
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 |