Cargando…
Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration
Gene therapy is one of the most promising approaches in regenerative medicine. Gene-activated matrices provide stable gene expression and the production of osteogenic proteins in situ to stimulate osteogenesis and bone repair. In this study, we developed new gene-activated matrices based on polylact...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9735524/ https://www.ncbi.nlm.nih.gov/pubmed/36499056 http://dx.doi.org/10.3390/ijms232314720 |
_version_ | 1784846787739123712 |
---|---|
author | Nedorubova, Irina Alekseevna Bukharova, Tatiana Borisovna Mokrousova, Viktoria Olegovna Khvorostina, Maria Aleksandrovna Vasilyev, Andrey Vyacheslavovich Nedorubov, Andrey Anatolevich Grigoriev, Timofei Evgenevich Zagoskin, Yuriy Dmitrievich Chvalun, Sergei Nicolaevich Kutsev, Sergey Ivanovich Goldshtein, Dmitry Vadimovich |
author_facet | Nedorubova, Irina Alekseevna Bukharova, Tatiana Borisovna Mokrousova, Viktoria Olegovna Khvorostina, Maria Aleksandrovna Vasilyev, Andrey Vyacheslavovich Nedorubov, Andrey Anatolevich Grigoriev, Timofei Evgenevich Zagoskin, Yuriy Dmitrievich Chvalun, Sergei Nicolaevich Kutsev, Sergey Ivanovich Goldshtein, Dmitry Vadimovich |
author_sort | Nedorubova, Irina Alekseevna |
collection | PubMed |
description | Gene therapy is one of the most promising approaches in regenerative medicine. Gene-activated matrices provide stable gene expression and the production of osteogenic proteins in situ to stimulate osteogenesis and bone repair. In this study, we developed new gene-activated matrices based on polylactide granules (PLA) impregnated with BMP2 polyplexes and included in chitosan hydrogel or PRP-based fibrin hydrogel. The matrices showed high biocompatibility both in vitro with mesenchymal stem cells and in vivo when implanted intramuscularly in rats. The use of porous PLA granules allowed the inclusion of a high concentration of polyplexes, and the introduction of the granules into hydrogel provided the gradual release of the plasmid constructs. All gene-activated matrices showed transfecting ability and ensured long-term gene expression and the production of target proteins in vitro. At the same time, the achieved concentration of BMP-2 was sufficient to induce osteogenic differentiation of MSCs. When implanted into critical-size calvarial defects in rats, all matrices with BMP2 polyplexes led to new bone formation. The most significant effect on osteoinduction was observed for the PLA/PRP matrices. Thus, the developed gene-activated matrices were shown to be safe and effective osteoplastic materials. PLA granules and PRP-based fibrin hydrogel containing BMP2 polyplexes were shown to be the most promising for future applications in bone regeneration. |
format | Online Article Text |
id | pubmed-9735524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97355242022-12-11 Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration Nedorubova, Irina Alekseevna Bukharova, Tatiana Borisovna Mokrousova, Viktoria Olegovna Khvorostina, Maria Aleksandrovna Vasilyev, Andrey Vyacheslavovich Nedorubov, Andrey Anatolevich Grigoriev, Timofei Evgenevich Zagoskin, Yuriy Dmitrievich Chvalun, Sergei Nicolaevich Kutsev, Sergey Ivanovich Goldshtein, Dmitry Vadimovich Int J Mol Sci Article Gene therapy is one of the most promising approaches in regenerative medicine. Gene-activated matrices provide stable gene expression and the production of osteogenic proteins in situ to stimulate osteogenesis and bone repair. In this study, we developed new gene-activated matrices based on polylactide granules (PLA) impregnated with BMP2 polyplexes and included in chitosan hydrogel or PRP-based fibrin hydrogel. The matrices showed high biocompatibility both in vitro with mesenchymal stem cells and in vivo when implanted intramuscularly in rats. The use of porous PLA granules allowed the inclusion of a high concentration of polyplexes, and the introduction of the granules into hydrogel provided the gradual release of the plasmid constructs. All gene-activated matrices showed transfecting ability and ensured long-term gene expression and the production of target proteins in vitro. At the same time, the achieved concentration of BMP-2 was sufficient to induce osteogenic differentiation of MSCs. When implanted into critical-size calvarial defects in rats, all matrices with BMP2 polyplexes led to new bone formation. The most significant effect on osteoinduction was observed for the PLA/PRP matrices. Thus, the developed gene-activated matrices were shown to be safe and effective osteoplastic materials. PLA granules and PRP-based fibrin hydrogel containing BMP2 polyplexes were shown to be the most promising for future applications in bone regeneration. MDPI 2022-11-25 /pmc/articles/PMC9735524/ /pubmed/36499056 http://dx.doi.org/10.3390/ijms232314720 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nedorubova, Irina Alekseevna Bukharova, Tatiana Borisovna Mokrousova, Viktoria Olegovna Khvorostina, Maria Aleksandrovna Vasilyev, Andrey Vyacheslavovich Nedorubov, Andrey Anatolevich Grigoriev, Timofei Evgenevich Zagoskin, Yuriy Dmitrievich Chvalun, Sergei Nicolaevich Kutsev, Sergey Ivanovich Goldshtein, Dmitry Vadimovich Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration |
title | Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration |
title_full | Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration |
title_fullStr | Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration |
title_full_unstemmed | Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration |
title_short | Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration |
title_sort | comparative efficiency of gene-activated matrices based on chitosan hydrogel and prp impregnated with bmp2 polyplexes for bone regeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9735524/ https://www.ncbi.nlm.nih.gov/pubmed/36499056 http://dx.doi.org/10.3390/ijms232314720 |
work_keys_str_mv | AT nedorubovairinaalekseevna comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration AT bukharovatatianaborisovna comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration AT mokrousovaviktoriaolegovna comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration AT khvorostinamariaaleksandrovna comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration AT vasilyevandreyvyacheslavovich comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration AT nedorubovandreyanatolevich comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration AT grigorievtimofeievgenevich comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration AT zagoskinyuriydmitrievich comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration AT chvalunsergeinicolaevich comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration AT kutsevsergeyivanovich comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration AT goldshteindmitryvadimovich comparativeefficiencyofgeneactivatedmatricesbasedonchitosanhydrogelandprpimpregnatedwithbmp2polyplexesforboneregeneration |