After fracture, mesenchymal stem cells (MSCs) and growth factors migrate into the fracture callus to exert their biological actions. Previous studies have indicated that dynamic loading induced tissue deformation and interstitial fluid flow could produce a biomechanical environment which significantly affects the healing outcomes. However, the fundamental relationship between the various loading regimes and different healing outcomes has not still been fully understood. In this study, we present an integrated computational model to investigate the effect of dynamic loading on early stage of bone fracture healing. The model takes into account cell and growth factor transport under dynamic loading, and mechanical stimuli mediated MSC differentiation and tissue production. The developed model was firstly validated by the available experimental data, and then implemented to identify the loading regimes that produce the optimal healing outcomes. Our results demonstrated that dynamic loading enhances MSC and growth factor transport in a spatially dependent manner. For example, compared to free diffusion, dynamic loading could significantly increase MSCs concentration in endosteal zone; and chondrogenic growth factors in both cortical and periosteal zones in callus. Furthermore, there could be an optimal dynamic loading regime (e.g. 10% strain at 1Hz) which could potentially significant enhance endochondral ossification.
机构:
Delft Univ Technol, Fac Mech Maritime & Mat Engn, NL-2628 CD Delft, NetherlandsDelft Univ Technol, Fac Mech Maritime & Mat Engn, NL-2628 CD Delft, Netherlands
Andreykiv, A.
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van Keulen, F.
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Prendergast, P. J.
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Trinity Coll Dublin, Sch Engn, Trinity Ctr Bioengn, Dublin, IrelandDelft Univ Technol, Fac Mech Maritime & Mat Engn, NL-2628 CD Delft, Netherlands
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Univ Leeds, Rheumatol & Rehabil Res Unit, Leeds LS2 9NZ, W Yorkshire, EnglandUniv Leeds, Rheumatol & Rehabil Res Unit, Leeds LS2 9NZ, W Yorkshire, England
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Boston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USABoston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USA
Barnes, GL
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Kostenuik, PJ
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Boston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USABoston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USA
Kostenuik, PJ
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Gerstenfeld, LC
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Boston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USABoston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USA
Gerstenfeld, LC
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Einhorn, TA
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Boston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USABoston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USA
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
Bonassar, LJ
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Grodzinsky, AJ
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机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
Grodzinsky, AJ
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Frank, EH
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机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
Frank, EH
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Davila, SG
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机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
Davila, SG
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Bhaktav, NR
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机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
Bhaktav, NR
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Trippel, SB
论文数: 0引用数: 0
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机构:
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USAHarvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
机构:
Delft Univ Technol, Fac Mech Maritime & Mat Engn, NL-2628 CD Delft, NetherlandsDelft Univ Technol, Fac Mech Maritime & Mat Engn, NL-2628 CD Delft, Netherlands
Andreykiv, A.
;
论文数: 引用数:
h-index:
机构:
van Keulen, F.
;
Prendergast, P. J.
论文数: 0引用数: 0
h-index: 0
机构:
Trinity Coll Dublin, Sch Engn, Trinity Ctr Bioengn, Dublin, IrelandDelft Univ Technol, Fac Mech Maritime & Mat Engn, NL-2628 CD Delft, Netherlands
机构:
Univ Leeds, Rheumatol & Rehabil Res Unit, Leeds LS2 9NZ, W Yorkshire, EnglandUniv Leeds, Rheumatol & Rehabil Res Unit, Leeds LS2 9NZ, W Yorkshire, England
机构:
Boston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USABoston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USA
Barnes, GL
;
Kostenuik, PJ
论文数: 0引用数: 0
h-index: 0
机构:
Boston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USABoston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USA
Kostenuik, PJ
;
Gerstenfeld, LC
论文数: 0引用数: 0
h-index: 0
机构:
Boston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USABoston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USA
Gerstenfeld, LC
;
Einhorn, TA
论文数: 0引用数: 0
h-index: 0
机构:
Boston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USABoston Univ, Sch Med, Dept Orthopaed Surg, Musculoskeletal Res Lab, Boston, MA 02118 USA
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
Bonassar, LJ
;
Grodzinsky, AJ
论文数: 0引用数: 0
h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
Grodzinsky, AJ
;
Frank, EH
论文数: 0引用数: 0
h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
Frank, EH
;
Davila, SG
论文数: 0引用数: 0
h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
Davila, SG
;
Bhaktav, NR
论文数: 0引用数: 0
h-index: 0
机构:Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA
Bhaktav, NR
;
Trippel, SB
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USAHarvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Res Labs, Boston, MA 02114 USA