Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

Anja M Boos,1,* Annika Weigand,1,* Gloria Deschler,1 Thomas Gerber,2 Andreas Arkudas,1 Ulrich Kneser,1 Raymund E Horch,1 Justus P Beier11Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg FAU, Erlangen, 2Ins...

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Autores principales: Boos AM, Weig, A, Deschler G, Gerber T, Arkudas A, Kneser U, Horch RE, Beier JP
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Publicado: Dove Medical Press 2014
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spelling oai:doaj.org-article:792b731099a54b94bbbb3439c6595df72021-12-02T00:46:38ZAutologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model1178-2013https://doaj.org/article/792b731099a54b94bbbb3439c6595df72014-11-01T00:00:00Zhttp://www.dovepress.com/autologous-serum-improves-bone-formation-in-a-primary-stable-silica-em-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Anja M Boos,1,* Annika Weigand,1,* Gloria Deschler,1 Thomas Gerber,2 Andreas Arkudas,1 Ulrich Kneser,1 Raymund E Horch,1 Justus P Beier11Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg FAU, Erlangen, 2Institute of Physics, University of Rostock, Rostock, Germany *These authors contributed equally to this work Abstract: New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 µg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in order to engineer an axially vascularized primary stable bone replacement in clinically relevant size for free transplantation. Keywords: nanostructured bone substitute, bone tissue engineering, autologous serum, mesenchymal stem cells, recombinant human bone morphogenetic protein 2, sheep modelBoos AMWeigADeschler GGerber TArkudas AKneser UHorch REBeier JPDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 5317-5339 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Boos AM
Weig
A
Deschler G
Gerber T
Arkudas A
Kneser U
Horch RE
Beier JP
Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model
description Anja M Boos,1,* Annika Weigand,1,* Gloria Deschler,1 Thomas Gerber,2 Andreas Arkudas,1 Ulrich Kneser,1 Raymund E Horch,1 Justus P Beier11Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg FAU, Erlangen, 2Institute of Physics, University of Rostock, Rostock, Germany *These authors contributed equally to this work Abstract: New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 µg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in order to engineer an axially vascularized primary stable bone replacement in clinically relevant size for free transplantation. Keywords: nanostructured bone substitute, bone tissue engineering, autologous serum, mesenchymal stem cells, recombinant human bone morphogenetic protein 2, sheep model
format article
author Boos AM
Weig
A
Deschler G
Gerber T
Arkudas A
Kneser U
Horch RE
Beier JP
author_facet Boos AM
Weig
A
Deschler G
Gerber T
Arkudas A
Kneser U
Horch RE
Beier JP
author_sort Boos AM
title Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model
title_short Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model
title_full Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model
title_fullStr Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model
title_full_unstemmed Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model
title_sort autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhbmp-2 in the sheep model
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/792b731099a54b94bbbb3439c6595df7
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