Bone forming capacity of cell- and growth factor-based constructs at different ectopic implantation sites.

K. Ma, F. Yang, Sanne Karijn Both, H.J. Prins, M.N. Helder, J. Pan, F.Z. Cui, J.A. Jansen, J.J. van den Beucken

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Abstract

The aim of this study was to compare the effect of implantation site (i.e., subcutaneous, SQ vs. intramuscular, IM) on bone forming capacity of cell-based and growth factor-based scaffolds in athymic nude rats after an implantation period of 8 weeks. Cell-based scaffolds consisted of porous hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds seeded with either human adipose tissue-derived mesenchymal stem cells (AT-MSCs) only or both AT-MSCs and human umbilical vein endothelial cells (HUVECs), which were precultured in osteogenic medium for 7 days. Growth factor-based scaffolds consisted of porous HA/TCP scaffolds with 20 µg preadsorbed bone morphogenetic protein-2 (BMP-2). Histological and histomorphometrical analysis were used to assess bone formation. A differentiation experiment was performed in parallel to compare the in vitro osteogenic capacity of cell-based scaffolds. The results showed that cell-based scaffolds showed evident osteogenic differentiation in vitro, with only marginal differences between AT-MSCs only and AT-MSCs/HUVECs. In vivo, none of the cell-based scaffolds showed bone formation, irrespective of the site of implantation. In contrast, all growth factor-based scaffolds showed bone formation at both implantation sites without differences in the amount of formed bone. In conclusion, the results of this study demonstrated that the bone forming capacity of HA/TCP scaffolds with pre-adsorbed BMP-2 was equal at different ectopic implantation sites. Further, despite obvious in vitro osteogenic differentiation of AT-MSCs and AT-MSCS/HUVECs on HA/TCP scaffolds, no bone formation of these cell-based scaffolds was observed in vivo. This indicates further investigation on bone formation mechanisms of AT-MSCs is needed before AT-MSCs can be used as a cytotherapeutic treatment in clinics
Original languageEnglish
Pages (from-to)439-450
JournalJournal of biomedical materials research. Part A
Volume103
Issue number2
DOIs
Publication statusPublished - 22 Apr 2015

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Scaffolds
Intercellular Signaling Peptides and Proteins
Bone
Stem cells
Tissue
Hydroxyapatite
Durapatite
Endothelial cells
Phosphates
Bone Morphogenetic Protein 2
Scaffolds (biology)
Proteins
Rats
Cells
tricalcium phosphate

Keywords

  • IR-99049
  • METIS-314873

Cite this

Ma, K. ; Yang, F. ; Both, Sanne Karijn ; Prins, H.J. ; Helder, M.N. ; Pan, J. ; Cui, F.Z. ; Jansen, J.A. ; van den Beucken, J.J. / Bone forming capacity of cell- and growth factor-based constructs at different ectopic implantation sites. In: Journal of biomedical materials research. Part A. 2015 ; Vol. 103, No. 2. pp. 439-450.
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title = "Bone forming capacity of cell- and growth factor-based constructs at different ectopic implantation sites.",
abstract = "The aim of this study was to compare the effect of implantation site (i.e., subcutaneous, SQ vs. intramuscular, IM) on bone forming capacity of cell-based and growth factor-based scaffolds in athymic nude rats after an implantation period of 8 weeks. Cell-based scaffolds consisted of porous hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds seeded with either human adipose tissue-derived mesenchymal stem cells (AT-MSCs) only or both AT-MSCs and human umbilical vein endothelial cells (HUVECs), which were precultured in osteogenic medium for 7 days. Growth factor-based scaffolds consisted of porous HA/TCP scaffolds with 20 µg preadsorbed bone morphogenetic protein-2 (BMP-2). Histological and histomorphometrical analysis were used to assess bone formation. A differentiation experiment was performed in parallel to compare the in vitro osteogenic capacity of cell-based scaffolds. The results showed that cell-based scaffolds showed evident osteogenic differentiation in vitro, with only marginal differences between AT-MSCs only and AT-MSCs/HUVECs. In vivo, none of the cell-based scaffolds showed bone formation, irrespective of the site of implantation. In contrast, all growth factor-based scaffolds showed bone formation at both implantation sites without differences in the amount of formed bone. In conclusion, the results of this study demonstrated that the bone forming capacity of HA/TCP scaffolds with pre-adsorbed BMP-2 was equal at different ectopic implantation sites. Further, despite obvious in vitro osteogenic differentiation of AT-MSCs and AT-MSCS/HUVECs on HA/TCP scaffolds, no bone formation of these cell-based scaffolds was observed in vivo. This indicates further investigation on bone formation mechanisms of AT-MSCs is needed before AT-MSCs can be used as a cytotherapeutic treatment in clinics",
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Bone forming capacity of cell- and growth factor-based constructs at different ectopic implantation sites. / Ma, K.; Yang, F.; Both, Sanne Karijn; Prins, H.J.; Helder, M.N.; Pan, J.; Cui, F.Z.; Jansen, J.A.; van den Beucken, J.J.

In: Journal of biomedical materials research. Part A, Vol. 103, No. 2, 22.04.2015, p. 439-450.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Bone forming capacity of cell- and growth factor-based constructs at different ectopic implantation sites.

AU - Ma, K.

AU - Yang, F.

AU - Both, Sanne Karijn

AU - Prins, H.J.

AU - Helder, M.N.

AU - Pan, J.

AU - Cui, F.Z.

AU - Jansen, J.A.

AU - van den Beucken, J.J.

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N2 - The aim of this study was to compare the effect of implantation site (i.e., subcutaneous, SQ vs. intramuscular, IM) on bone forming capacity of cell-based and growth factor-based scaffolds in athymic nude rats after an implantation period of 8 weeks. Cell-based scaffolds consisted of porous hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds seeded with either human adipose tissue-derived mesenchymal stem cells (AT-MSCs) only or both AT-MSCs and human umbilical vein endothelial cells (HUVECs), which were precultured in osteogenic medium for 7 days. Growth factor-based scaffolds consisted of porous HA/TCP scaffolds with 20 µg preadsorbed bone morphogenetic protein-2 (BMP-2). Histological and histomorphometrical analysis were used to assess bone formation. A differentiation experiment was performed in parallel to compare the in vitro osteogenic capacity of cell-based scaffolds. The results showed that cell-based scaffolds showed evident osteogenic differentiation in vitro, with only marginal differences between AT-MSCs only and AT-MSCs/HUVECs. In vivo, none of the cell-based scaffolds showed bone formation, irrespective of the site of implantation. In contrast, all growth factor-based scaffolds showed bone formation at both implantation sites without differences in the amount of formed bone. In conclusion, the results of this study demonstrated that the bone forming capacity of HA/TCP scaffolds with pre-adsorbed BMP-2 was equal at different ectopic implantation sites. Further, despite obvious in vitro osteogenic differentiation of AT-MSCs and AT-MSCS/HUVECs on HA/TCP scaffolds, no bone formation of these cell-based scaffolds was observed in vivo. This indicates further investigation on bone formation mechanisms of AT-MSCs is needed before AT-MSCs can be used as a cytotherapeutic treatment in clinics

AB - The aim of this study was to compare the effect of implantation site (i.e., subcutaneous, SQ vs. intramuscular, IM) on bone forming capacity of cell-based and growth factor-based scaffolds in athymic nude rats after an implantation period of 8 weeks. Cell-based scaffolds consisted of porous hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds seeded with either human adipose tissue-derived mesenchymal stem cells (AT-MSCs) only or both AT-MSCs and human umbilical vein endothelial cells (HUVECs), which were precultured in osteogenic medium for 7 days. Growth factor-based scaffolds consisted of porous HA/TCP scaffolds with 20 µg preadsorbed bone morphogenetic protein-2 (BMP-2). Histological and histomorphometrical analysis were used to assess bone formation. A differentiation experiment was performed in parallel to compare the in vitro osteogenic capacity of cell-based scaffolds. The results showed that cell-based scaffolds showed evident osteogenic differentiation in vitro, with only marginal differences between AT-MSCs only and AT-MSCs/HUVECs. In vivo, none of the cell-based scaffolds showed bone formation, irrespective of the site of implantation. In contrast, all growth factor-based scaffolds showed bone formation at both implantation sites without differences in the amount of formed bone. In conclusion, the results of this study demonstrated that the bone forming capacity of HA/TCP scaffolds with pre-adsorbed BMP-2 was equal at different ectopic implantation sites. Further, despite obvious in vitro osteogenic differentiation of AT-MSCs and AT-MSCS/HUVECs on HA/TCP scaffolds, no bone formation of these cell-based scaffolds was observed in vivo. This indicates further investigation on bone formation mechanisms of AT-MSCs is needed before AT-MSCs can be used as a cytotherapeutic treatment in clinics

KW - IR-99049

KW - METIS-314873

U2 - 10.1002/jbm.a.35192

DO - 10.1002/jbm.a.35192

M3 - Article

VL - 103

SP - 439

EP - 450

JO - Journal of biomedical materials research. Part A

JF - Journal of biomedical materials research. Part A

SN - 1549-3296

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ER -