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Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering
The local release of complexed siRNA from biomaterials opens precisely targeted therapeutic options. In this study, complexed siRNA was loaded to gelatin microparticles cross-linked (cGM) with an anhydride-containing oligomer (oPNMA). We aggregated these siRNA-loaded cGM with human mesenchymal stem...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949427/ https://www.ncbi.nlm.nih.gov/pubmed/35335924 http://dx.doi.org/10.3390/pharmaceutics14030548 |
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author | Hinkelmann, Sandra Springwald, Alexandra H. Schulze, Sabine Hempel, Ute Mitrach, Franziska Wölk, Christian Hacker, Michael C. Schulz-Siegmund, Michaela |
author_facet | Hinkelmann, Sandra Springwald, Alexandra H. Schulze, Sabine Hempel, Ute Mitrach, Franziska Wölk, Christian Hacker, Michael C. Schulz-Siegmund, Michaela |
author_sort | Hinkelmann, Sandra |
collection | PubMed |
description | The local release of complexed siRNA from biomaterials opens precisely targeted therapeutic options. In this study, complexed siRNA was loaded to gelatin microparticles cross-linked (cGM) with an anhydride-containing oligomer (oPNMA). We aggregated these siRNA-loaded cGM with human mesenchymal stem cells (hMSC) to microtissues and stimulated them with osteogenic supplements. An efficient knockdown of chordin, a BMP-2 antagonist, caused a remarkably increased alkaline phosphatase (ALP) activity in the microtissues. cGM, as a component of microtissues, mineralized in a differentiation medium within 8–9 days, both in the presence and in the absence of cells. In order to investigate the effects of our pre-differentiated and chordin-silenced microtissues on bone homeostasis, we simulated in vivo conditions in an unstimulated co-culture system of hMSC and human peripheral blood mononuclear cells (hPBMC). We found enhanced ALP activity and osteoprotegerin (OPG) secretion in the model system compared to control microtissues. Our results suggest osteoanabolic effects of pre-differentiated and chordin-silenced microtissues. |
format | Online Article Text |
id | pubmed-8949427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89494272022-03-26 Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering Hinkelmann, Sandra Springwald, Alexandra H. Schulze, Sabine Hempel, Ute Mitrach, Franziska Wölk, Christian Hacker, Michael C. Schulz-Siegmund, Michaela Pharmaceutics Article The local release of complexed siRNA from biomaterials opens precisely targeted therapeutic options. In this study, complexed siRNA was loaded to gelatin microparticles cross-linked (cGM) with an anhydride-containing oligomer (oPNMA). We aggregated these siRNA-loaded cGM with human mesenchymal stem cells (hMSC) to microtissues and stimulated them with osteogenic supplements. An efficient knockdown of chordin, a BMP-2 antagonist, caused a remarkably increased alkaline phosphatase (ALP) activity in the microtissues. cGM, as a component of microtissues, mineralized in a differentiation medium within 8–9 days, both in the presence and in the absence of cells. In order to investigate the effects of our pre-differentiated and chordin-silenced microtissues on bone homeostasis, we simulated in vivo conditions in an unstimulated co-culture system of hMSC and human peripheral blood mononuclear cells (hPBMC). We found enhanced ALP activity and osteoprotegerin (OPG) secretion in the model system compared to control microtissues. Our results suggest osteoanabolic effects of pre-differentiated and chordin-silenced microtissues. MDPI 2022-02-28 /pmc/articles/PMC8949427/ /pubmed/35335924 http://dx.doi.org/10.3390/pharmaceutics14030548 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 Hinkelmann, Sandra Springwald, Alexandra H. Schulze, Sabine Hempel, Ute Mitrach, Franziska Wölk, Christian Hacker, Michael C. Schulz-Siegmund, Michaela Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering |
title | Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering |
title_full | Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering |
title_fullStr | Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering |
title_full_unstemmed | Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering |
title_short | Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering |
title_sort | mineralizing gelatin microparticles as cell carrier and drug delivery system for sirna for bone tissue engineering |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949427/ https://www.ncbi.nlm.nih.gov/pubmed/35335924 http://dx.doi.org/10.3390/pharmaceutics14030548 |
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