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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...

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Autores principales: 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
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
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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.
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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
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