Uniaxial Mechanical Strain: An In Vitro Correlate to Distraction Osteogenesis

Bhatt, Kirit A.; Chang, Eric I.; Lin, Shin-e; Bastidas, Nicholas; Ghali, Shadi; Thibboneir, Aurelia; Capla, Jennifer M.; McCarthy, Joseph G.; Gurtner, Geoffrey C.

doi:10.1016/j.jss.2007.01.023

Cited by 59 publications

(64 citation statements)

References 33 publications

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“…1,6,12,14,15,[47][48][49] Studies by Simmoms et al have shown that mesenchymal stem cells produced increased calcium accumulation in response to 3% strain (0.25 Hz). 50 Other studies have demonstrated that a 1% magnitude of cyclic uniaxial tensile stress with 1 Hz frequency increased OPN, ALP, and OCN mRNA 47 and 3% strain (1 Hz) induced osteonectin mRNA.…”

Section: Tensile Stress and Gfs For Bone Tissue Engineeringmentioning

confidence: 99%

“…M echanosignals generated by strain modulation can control diverse cell activities such as proliferation, 1 migration, 1 and differentiation. 2 In vitro strain modulation has been investigated as a promising mechanical cue for regeneration of bone, 3 tendon, 4 and blood vessels.…”

Section: Introductionmentioning

confidence: 99%

“…3,6,7 This bioreactor has applied 5%-10% elongation with 0.2-1 Hz frequency to 3D scaffolds including polyurethane nanofibrous scaffolds, 8 and fibrin, 9 and collagen gels. 10 Tensile stress of 3%-20% magnitude modulated expression of bone-related molecules such as collagen, 7,11 osteocalcin (OCN), 1,7 osteopontin (OPN), 1,7 matrix metalloproteinase-13 (MMP-13), 12 osteoprotegerin (OPG), 6 prostaglandin E 2 (PGE 2 ), 13 cyclooxygenase-2 (COX-2), 14 vascular endothelial growth factor (VEGF), 1,15 and transforming growth factor-b1 (TGF-b1). 16 Other external stimulating factors for bone regeneration are osteoinductive growth factors (GFs) such as TGF, bone morphogenetic protein (BMP), and platelet-derived GF.…”

Section: Introductionmentioning

confidence: 99%

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Response of a Preosteoblastic Cell Line to Cyclic Tensile Stress Conditioning and Growth Factors for Bone Tissue Engineering

Chung

Rylander²

2012

Tissue Engineering Part A

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Bone regeneration can be accelerated by utilizing mechanical stress and growth factors (GFs). However, a limited understanding exists regarding the response of preosteoblasts to tensile stress alone or with GFs. We measured cell proliferation and expression of heat-shock proteins (HSPs) and other bone-related proteins by preosteoblasts following cyclic tensile stress (1%-10% magnitude) alone or in combination with bone morphogenetic protein-2 (BMP-2) and transforming growth factor-b1 (TGF-b1). Tensile stress (3%) with GFs induced greater gene upregulation of osteoprotegerin (3.3 relative fold induction [RFI] compared to sham-treated samples), prostaglandin E synthase 2 (2.1 RFI), and vascular endothelial growth factor (VEGF) (11.5 RFI), compared with samples treated with stimuli alone or sham-treated samples. The most significant increases in messenger RNA expression occurred with GF addition to either static-cultured or tensile-loaded (1% elongation) cells for the following genes: HSP47 (RFI = 2.53), cyclooxygenase-2 (RFI = 72.52), bone sialoprotein (RFI = 11.56), and TGF-b1 (RFI = 8.05). Following 5% strain with GFs, VEGF secretion increased 64% (days 3-6) compared with GF alone and cell proliferation increased 23% compared with the sham-treated group. GF addition increased osteocalcin secretion but decreased matrix metalloproteinase-9 significantly (days 3-6). Tensile stress and GFs in combination may enhance bone regeneration by initiating angiogenic and anti-osteoclastic effects and promote cell growth.

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Section: Tensile Stress and Gfs For Bone Tissue Engineeringmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Response of a Preosteoblastic Cell Line to Cyclic Tensile Stress Conditioning and Growth Factors for Bone Tissue Engineering

Chung

Rylander²

2012

Tissue Engineering Part A

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“…9,28,29 In vitro loading of bone-derived cells RM Delaine-Smith et al parameters vary from 0.05 to 1 Hz and 1 to 12% uniaxial strain (up to 120 000 me). [38][39][40] The concave nature of the FlexCell engenders heterogeneous strain 38,41 and the viscoelastic properties mean that specific calibration curves must be determined for each test. 42 Specific materials: Flexcell FX-5000 Tension System (Flexcell International Corporation); BioFlex, Tissue Train, UniFlex or HT BioFlex culture plates (Flexcell International Corporation).…”

Section: Flexcell Tension Systemmentioning

confidence: 99%

“…A vacuum underneath the well draws down the rubber seal beneath the FlexCell and in doing so causes stretch to occur beneath the cells. [37][38][39][40][41][42] For the in vitro four-point bending jig, (b) osteoblasts were seeded as a monolayer onto the custom-made plastic slides and bathed in media in the jig apparatus housed in a 37 1C incubator with 5% CO 2 . (c) The cells experience a strain of 3400 me over a period of 10 min during which the slide is deformed 600 times.…”

Section: Loading Postmentioning

confidence: 99%

Preclinical models for in vitro mechanical loading of bone-derived cells

Delaine-Smith¹,

Javaheri²,

Edwards³

et al. 2015

BoneKEy Reports

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It is well established that bone responds to mechanical stimuli whereby physical forces are translated into chemical signals between cells, via mechanotransduction. It is difficult however to study the precise cellular and molecular responses using in vivo systems. In vitro loading models, which aim to replicate forces found within the bone microenvironment, make the underlying processes of mechanotransduction accessible to the researcher. Direct measurements in vivo and predictive modeling have been used to define these forces in normal physiological and pathological states. The types of mechanical stimuli present in the bone include vibration, fluid shear, substrate deformation and compressive loading, which can all be applied in vitro to monolayer and three-dimensional (3D) cultures. In monolayer, vibration can be readily applied to cultures via a low-magnitude, high-frequency loading rig. Fluid shear can be applied to cultures in multiwell plates via a simple rocking platform to engender gravitational fluid movement or via a pump to cells attached to a slide within a parallel-plate flow chamber, which may be micropatterned for use with osteocytes. Substrate strain can be applied via the vacuum-driven FlexCell system or via a four-point loading jig. 3D cultures better replicate the bone microenvironment and can also be subjected to the same forms of mechanical stimuli as monolayer, including vibration, fluid shear via perfusion flow, strain or compression. 3D cocultures that more closely replicate the bone microenvironment can be used to study the collective response of several cell types to loading. This technical review summarizes the methods for applying mechanical stimuli to bone cells in vitro.

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Multiphysics simulation of a compression–perfusion combined bioreactor to predict the mechanical microenvironment during bone metastatic breast cancer loading experiments

Liu

Han

Modarres‐Sadeghi

et al. 2021

Biotech & Bioengineering

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Incurable breast cancer bone metastasis causes widespread bone loss, resulting in fragility, pain, increased fracture risk, and ultimately increased patient mortality. Increased mechanical signals in the skeleton are anabolic and protect against bone loss, and they may also do so during osteolytic bone metastasis. Skeletal mechanical signals include interdependent tissue deformations and interstitial fluid flow, but how metastatic tumor cells respond to each of these individual signals remains underinvestigated, a barrier to translation to the clinic. To delineate their respective roles, we report computed estimates of the internal mechanical field of a bone mimetic scaffold undergoing combinations of high and low compression and perfusion using multiphysics simulations. Simulations were conducted in advance of multimodal loading bioreactor experiments with bone metastatic breast cancer cells to ensure that mechanical stimuli occurring internally were physiological and anabolic. Our results show that mechanical stimuli throughout the scaffold were within the anabolic range of bone cells in all loading configurations, were homogenously distributed throughout, and that combined high magnitude compression and perfusion synergized to produce the largest wall shear stresses within the scaffold. These simulations, when combined with experiments, will shed light on how increased mechanical loading in the skeleton may confer anti‐tumorigenic effects during metastasis.

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Uniaxial Mechanical Strain: An In Vitro Correlate to Distraction Osteogenesis

Cited by 59 publications

References 33 publications

Response of a Preosteoblastic Cell Line to Cyclic Tensile Stress Conditioning and Growth Factors for Bone Tissue Engineering

Response of a Preosteoblastic Cell Line to Cyclic Tensile Stress Conditioning and Growth Factors for Bone Tissue Engineering

Preclinical models for in vitro mechanical loading of bone-derived cells

Multiphysics simulation of a compression–perfusion combined bioreactor to predict the mechanical microenvironment during bone metastatic breast cancer loading experiments

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