Non-invasive time-lapsed monitoring and quantification of engineered bone-like tissue

H. Hagenmüller, S. Hofmann, T. Kohler, H.P. Merkle, D.L. Kaplan, G. Vunjak-Novakovic, R. Müller, L. Meinel

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Abstract

The formation of bone-like tissue from human mesenchymal stem cells (hMSC) cultured in osteogenic medium on silk fibroin scaffolds was monitored and quantified over 44 days in culture using non-invasive time-lapsed micro-computed tomography (µCT). Each construct was imaged nine times in situ. From µCT imaging, detailed morphometrical data on bone volume density, surface-to-volume ratio, trabecular thickness, trabecular spacing, and the structure model index and tissue mineral density were obtained. µCT irradiation did not impact the osteogenic performance of hMSCs based on DNA content, alkaline phosphatase activity, and calcium deposition when compared to non-exposed control samples. Bone-like tissue formation initiated at day 10 of the culture with the deposition of small mineralized clusters. Tissue mineral density increased linearly over time. The surface-to-volume ratio of the bone-like tissues converged asymptotically to 26 mm-1. Although in vitro formation of bone-like tissue started from clusters, the overall bone volume was not predictable from the time, number, and size of initially formed bone-like clusters. Based on microstructural analysis, the morphometry of the tissue-engineered constructs was found to be in the range of human trabecular bone. In future studies, non-invasive, time-lapsed monitoring may enable researchers to culture tissues in vitro, right until the development of a desired morphology is accomplished. Our data demonstrate the feasibility of qualitatively and quantitatively detailing the spatial and temporal mineralization of bone-like tissue formation in tissue engineering. © 2007 Biomedical Engineering Society.
Original languageEnglish
Pages (from-to)1657-1667
Number of pages11
JournalAnnals of Biomedical Engineering
Volume35
Issue number10
DOIs
Publication statusPublished - 2007
Externally publishedYes

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Bone
Tissue
Monitoring
Tomography
Minerals
Tissue culture
Biomedical engineering
Phosphatases
Silk
Model structures
Stem cells
Tissue engineering
Scaffolds
Calcium
DNA
Irradiation
Imaging techniques

Cite this

Hagenmüller, H., Hofmann, S., Kohler, T., Merkle, H. P., Kaplan, D. L., Vunjak-Novakovic, G., ... Meinel, L. (2007). Non-invasive time-lapsed monitoring and quantification of engineered bone-like tissue. Annals of Biomedical Engineering, 35(10), 1657-1667. https://doi.org/10.1007/s10439-007-9338-2
Hagenmüller, H. ; Hofmann, S. ; Kohler, T. ; Merkle, H.P. ; Kaplan, D.L. ; Vunjak-Novakovic, G. ; Müller, R. ; Meinel, L. / Non-invasive time-lapsed monitoring and quantification of engineered bone-like tissue. In: Annals of Biomedical Engineering. 2007 ; Vol. 35, No. 10. pp. 1657-1667.
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Hagenmüller, H, Hofmann, S, Kohler, T, Merkle, HP, Kaplan, DL, Vunjak-Novakovic, G, Müller, R & Meinel, L 2007, 'Non-invasive time-lapsed monitoring and quantification of engineered bone-like tissue', Annals of Biomedical Engineering, vol. 35, no. 10, pp. 1657-1667. https://doi.org/10.1007/s10439-007-9338-2

Non-invasive time-lapsed monitoring and quantification of engineered bone-like tissue. / Hagenmüller, H.; Hofmann, S.; Kohler, T.; Merkle, H.P.; Kaplan, D.L.; Vunjak-Novakovic, G.; Müller, R.; Meinel, L.

In: Annals of Biomedical Engineering, Vol. 35, No. 10, 2007, p. 1657-1667.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Non-invasive time-lapsed monitoring and quantification of engineered bone-like tissue

AU - Hagenmüller, H.

AU - Hofmann, S.

AU - Kohler, T.

AU - Merkle, H.P.

AU - Kaplan, D.L.

AU - Vunjak-Novakovic, G.

AU - Müller, R.

AU - Meinel, L.

PY - 2007

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N2 - The formation of bone-like tissue from human mesenchymal stem cells (hMSC) cultured in osteogenic medium on silk fibroin scaffolds was monitored and quantified over 44 days in culture using non-invasive time-lapsed micro-computed tomography (µCT). Each construct was imaged nine times in situ. From µCT imaging, detailed morphometrical data on bone volume density, surface-to-volume ratio, trabecular thickness, trabecular spacing, and the structure model index and tissue mineral density were obtained. µCT irradiation did not impact the osteogenic performance of hMSCs based on DNA content, alkaline phosphatase activity, and calcium deposition when compared to non-exposed control samples. Bone-like tissue formation initiated at day 10 of the culture with the deposition of small mineralized clusters. Tissue mineral density increased linearly over time. The surface-to-volume ratio of the bone-like tissues converged asymptotically to 26 mm-1. Although in vitro formation of bone-like tissue started from clusters, the overall bone volume was not predictable from the time, number, and size of initially formed bone-like clusters. Based on microstructural analysis, the morphometry of the tissue-engineered constructs was found to be in the range of human trabecular bone. In future studies, non-invasive, time-lapsed monitoring may enable researchers to culture tissues in vitro, right until the development of a desired morphology is accomplished. Our data demonstrate the feasibility of qualitatively and quantitatively detailing the spatial and temporal mineralization of bone-like tissue formation in tissue engineering. © 2007 Biomedical Engineering Society.

AB - The formation of bone-like tissue from human mesenchymal stem cells (hMSC) cultured in osteogenic medium on silk fibroin scaffolds was monitored and quantified over 44 days in culture using non-invasive time-lapsed micro-computed tomography (µCT). Each construct was imaged nine times in situ. From µCT imaging, detailed morphometrical data on bone volume density, surface-to-volume ratio, trabecular thickness, trabecular spacing, and the structure model index and tissue mineral density were obtained. µCT irradiation did not impact the osteogenic performance of hMSCs based on DNA content, alkaline phosphatase activity, and calcium deposition when compared to non-exposed control samples. Bone-like tissue formation initiated at day 10 of the culture with the deposition of small mineralized clusters. Tissue mineral density increased linearly over time. The surface-to-volume ratio of the bone-like tissues converged asymptotically to 26 mm-1. Although in vitro formation of bone-like tissue started from clusters, the overall bone volume was not predictable from the time, number, and size of initially formed bone-like clusters. Based on microstructural analysis, the morphometry of the tissue-engineered constructs was found to be in the range of human trabecular bone. In future studies, non-invasive, time-lapsed monitoring may enable researchers to culture tissues in vitro, right until the development of a desired morphology is accomplished. Our data demonstrate the feasibility of qualitatively and quantitatively detailing the spatial and temporal mineralization of bone-like tissue formation in tissue engineering. © 2007 Biomedical Engineering Society.

U2 - 10.1007/s10439-007-9338-2

DO - 10.1007/s10439-007-9338-2

M3 - Article

C2 - 17546503

VL - 35

SP - 1657

EP - 1667

JO - Annals of Biomedical Engineering

JF - Annals of Biomedical Engineering

SN - 0090-6964

IS - 10

ER -