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Gelatin-Modified Calcium/Strontium Hydrogen Phosphates Stimulate Bone Regeneration in Osteoblast/Osteoclast Co-Culture and in Osteoporotic Rat Femur Defects—In Vitro to In Vivo Translation
The development and characterization of biomaterials for bone replacement in case of large defects in preconditioned bone (e.g., osteoporosis) require close cooperation of various disciplines. Of particular interest are effects observed in vitro at the cellular level and their in vivo representation...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662833/ https://www.ncbi.nlm.nih.gov/pubmed/33153127 http://dx.doi.org/10.3390/molecules25215103 |
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author | Kruppke, Benjamin Ray, Seemun Alt, Volker Rohnke, Marcus Kern, Christine Kampschulte, Marian Heinemann, Christiane Budak, Matthäus Adam, Josephine Döhner, Nils Franz-Forsthoffer, Lucretia El Khassawna, Thaqif Heiss, Christian Hanke, Thomas Thormann, Ulrich |
author_facet | Kruppke, Benjamin Ray, Seemun Alt, Volker Rohnke, Marcus Kern, Christine Kampschulte, Marian Heinemann, Christiane Budak, Matthäus Adam, Josephine Döhner, Nils Franz-Forsthoffer, Lucretia El Khassawna, Thaqif Heiss, Christian Hanke, Thomas Thormann, Ulrich |
author_sort | Kruppke, Benjamin |
collection | PubMed |
description | The development and characterization of biomaterials for bone replacement in case of large defects in preconditioned bone (e.g., osteoporosis) require close cooperation of various disciplines. Of particular interest are effects observed in vitro at the cellular level and their in vivo representation in animal experiments. In the present case, the material-based alteration of the ratio of osteoblasts to osteoclasts in vitro in the context of their co-cultivation was examined and showed equivalence to the material-based stimulation of bone regeneration in a bone defect of osteoporotic rats. Gelatin-modified calcium/strontium phosphates with a Ca:Sr ratio in their precipitation solutions of 5:5 and 3:7 caused a pro-osteogenic reaction on both levels in vitro and in vivo. Stimulation of osteoblasts and inhibition of osteoclast activity were proven during culture on materials with higher strontium content. The same material caused a decrease in osteoclast activity in vitro. In vivo, a positive effect of the material with increased strontium content was observed by immunohistochemistry, e.g., by significantly increased bone volume to tissue volume ratio, increased bone morphogenetic protein-2 (BMP2) expression, and significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. In addition, material degradation and bone regeneration were examined after 6 weeks using stage scans with ToF-SIMS and µ-CT imaging. The remaining material in the defects and strontium signals, which originate from areas exceeding the defect area, indicate the incorporation of strontium ions into the surrounding mineralized tissue. Thus, the material inherent properties (release of biologically active ions, solubility and degradability, mechanical strength) directly influenced the cellular reaction in vitro and also bone regeneration in vivo. Based on this, in the future, materials might be synthesized and specifically adapted to patient-specific needs and their bone status. |
format | Online Article Text |
id | pubmed-7662833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76628332020-11-14 Gelatin-Modified Calcium/Strontium Hydrogen Phosphates Stimulate Bone Regeneration in Osteoblast/Osteoclast Co-Culture and in Osteoporotic Rat Femur Defects—In Vitro to In Vivo Translation Kruppke, Benjamin Ray, Seemun Alt, Volker Rohnke, Marcus Kern, Christine Kampschulte, Marian Heinemann, Christiane Budak, Matthäus Adam, Josephine Döhner, Nils Franz-Forsthoffer, Lucretia El Khassawna, Thaqif Heiss, Christian Hanke, Thomas Thormann, Ulrich Molecules Article The development and characterization of biomaterials for bone replacement in case of large defects in preconditioned bone (e.g., osteoporosis) require close cooperation of various disciplines. Of particular interest are effects observed in vitro at the cellular level and their in vivo representation in animal experiments. In the present case, the material-based alteration of the ratio of osteoblasts to osteoclasts in vitro in the context of their co-cultivation was examined and showed equivalence to the material-based stimulation of bone regeneration in a bone defect of osteoporotic rats. Gelatin-modified calcium/strontium phosphates with a Ca:Sr ratio in their precipitation solutions of 5:5 and 3:7 caused a pro-osteogenic reaction on both levels in vitro and in vivo. Stimulation of osteoblasts and inhibition of osteoclast activity were proven during culture on materials with higher strontium content. The same material caused a decrease in osteoclast activity in vitro. In vivo, a positive effect of the material with increased strontium content was observed by immunohistochemistry, e.g., by significantly increased bone volume to tissue volume ratio, increased bone morphogenetic protein-2 (BMP2) expression, and significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. In addition, material degradation and bone regeneration were examined after 6 weeks using stage scans with ToF-SIMS and µ-CT imaging. The remaining material in the defects and strontium signals, which originate from areas exceeding the defect area, indicate the incorporation of strontium ions into the surrounding mineralized tissue. Thus, the material inherent properties (release of biologically active ions, solubility and degradability, mechanical strength) directly influenced the cellular reaction in vitro and also bone regeneration in vivo. Based on this, in the future, materials might be synthesized and specifically adapted to patient-specific needs and their bone status. MDPI 2020-11-03 /pmc/articles/PMC7662833/ /pubmed/33153127 http://dx.doi.org/10.3390/molecules25215103 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kruppke, Benjamin Ray, Seemun Alt, Volker Rohnke, Marcus Kern, Christine Kampschulte, Marian Heinemann, Christiane Budak, Matthäus Adam, Josephine Döhner, Nils Franz-Forsthoffer, Lucretia El Khassawna, Thaqif Heiss, Christian Hanke, Thomas Thormann, Ulrich Gelatin-Modified Calcium/Strontium Hydrogen Phosphates Stimulate Bone Regeneration in Osteoblast/Osteoclast Co-Culture and in Osteoporotic Rat Femur Defects—In Vitro to In Vivo Translation |
title | Gelatin-Modified Calcium/Strontium Hydrogen Phosphates Stimulate Bone Regeneration in Osteoblast/Osteoclast Co-Culture and in Osteoporotic Rat Femur Defects—In Vitro to In Vivo Translation |
title_full | Gelatin-Modified Calcium/Strontium Hydrogen Phosphates Stimulate Bone Regeneration in Osteoblast/Osteoclast Co-Culture and in Osteoporotic Rat Femur Defects—In Vitro to In Vivo Translation |
title_fullStr | Gelatin-Modified Calcium/Strontium Hydrogen Phosphates Stimulate Bone Regeneration in Osteoblast/Osteoclast Co-Culture and in Osteoporotic Rat Femur Defects—In Vitro to In Vivo Translation |
title_full_unstemmed | Gelatin-Modified Calcium/Strontium Hydrogen Phosphates Stimulate Bone Regeneration in Osteoblast/Osteoclast Co-Culture and in Osteoporotic Rat Femur Defects—In Vitro to In Vivo Translation |
title_short | Gelatin-Modified Calcium/Strontium Hydrogen Phosphates Stimulate Bone Regeneration in Osteoblast/Osteoclast Co-Culture and in Osteoporotic Rat Femur Defects—In Vitro to In Vivo Translation |
title_sort | gelatin-modified calcium/strontium hydrogen phosphates stimulate bone regeneration in osteoblast/osteoclast co-culture and in osteoporotic rat femur defects—in vitro to in vivo translation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662833/ https://www.ncbi.nlm.nih.gov/pubmed/33153127 http://dx.doi.org/10.3390/molecules25215103 |
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