Influence of Shear Stress in Perfusion Bioreactor Cultures for the Development of Three-Dimensional Bone Tissue Constructs: A Review

McCoy, Ryan; O’Brien, Fergal J.

doi:10.1089/ten.teb.2010.0370

Cited by 181 publications

(214 citation statements)

References 135 publications

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“…Lastly, OFF can stimulate the mineralization of cells by enhanced nutrient distribution and oxygen transportation to cells in scaffolds compared to static culture (McCoy & O'Brien, 2010). The electrospun PCL scaffolds in this study are thin (300‐μm thickness) compared to typical porous scaffolds subjected to bioreactor culture therefore nutrient diffusion should be less of a limitation to static culture compared to other studies.…”

Section: Discussionmentioning

confidence: 99%

A simple rocker‐induced mechanical stimulus upregulates mineralization by human osteoprogenitor cells in fibrous scaffolds

Puwanun

Delaine-Smith

Colley

et al. 2017

J Tissue Eng Regen Med

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Biodegradable electrospun polycaprolactone scaffolds can be used to support bone‐forming cells and could fill a thin bony defect, such as in cleft palate. Oscillatory fluid flow has been shown to stimulate bone production in human progenitor cells in monolayer culture. The aim of this study was to examine whether bone matrix production by primary human mesenchymal stem cells from bone marrow or jaw periosteal tissue could be stimulated using oscillatory fluid flow supplied by a standard see‐saw rocker. This was investigated for cells in two‐dimensional culture and within electrospun polycaprolactone scaffolds. From day 4 of culture onwards, samples were rocked at 45 cycles/min for 1 h/day, 5 days/week (rocking group). Cell viability, calcium deposition, collagen production, alkaline phosphatase activity and vascular endothelial growth factor secretion were evaluated to assess the ability of the cells to undergo bone differentiation and induce vascularisation. Both cell types produced more mineralized tissue when subjected to rocking and supplemented with dexamethasone. Mesenchymal progenitors and primary human mesenchymal stem cells from bone marrow in three‐dimensional scaffolds upregulated mineral deposition after rocking culture as assessed by micro‐computed tomography and alizarin red staining. Interestingly, vascular endothelial growth factor secretion, which has previously been shown to be mechanically sensitive, was not altered by rocking in this system and was inhibited by dexamethasone. Rocker culture may be a cost effective, simple pretreatment for bone tissue engineering for small defects such as cleft palate.

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Section: Discussionmentioning

confidence: 99%

A simple rocker‐induced mechanical stimulus upregulates mineralization by human osteoprogenitor cells in fibrous scaffolds

Puwanun

Delaine-Smith

Colley

et al. 2017

J Tissue Eng Regen Med

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“…In 2D, osteogenic differentiation is enhanced at  in the range of 0.1-1.5Pa, typically well below the lower limit associated with cell detachment (1-100Pa) (McCoy and O'Brien, 2010). In highly porous scaffolds, osteogenesis can be promoted at much lower  (~1-100x10 -3 Pa), yet cell loss is a prevalent issue (McCoy and O'Brien, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…In highly porous scaffolds, osteogenesis can be promoted at much lower  (~1-100x10 -3 Pa), yet cell loss is a prevalent issue (McCoy and O'Brien, 2010). The overall goal of this paper was to firstly characterise cell detachment in response to fluid flow from highly porous CG scaffolds with different mean pore sizes, and secondly, to evaluate if the cell loss observed could be related to cell morphology and cell deformation.…”

Section: Discussionmentioning

confidence: 99%

“…During bioreactor culture, six constructs (n=2 per mean pore size) were cultured simultaneously using a steady flow regime for 6, 24 or 48h, at either 0.05, 1 or 5mL/min. These flow-rates were chosen as they equate to  between 9x10 -4 and 8.79x10 -1 Pa, values below that shown to stimulate or cause cell detachment of flatly attached cells in 2D (McCoy and O'Brien, 2010). Thus cell detachment would be expected to be predominantly related to bridged cells.…”

Section: Bioreactor Experimentsmentioning

confidence: 99%

“…Computational modelling has shown that bridged cells can experience up to 500 fold greater levels of cytoskeletal deformation than flat cells under the same flow conditions (Jungreuthmayer et al, 2009b); their alignment to the direction of flow creates a greater level of resistance and at the extreme end of the scale one can consider them to behave like a sail in the wind. We hypothesise it is this increased cytoskeletal deformation of bridging cells that promotes osteogenesis at lower mean shear stress levels () (~1-100x10 -3 Pa) in highly porous scaffolds compared to 2D (0.1-1.5Pa) (McCoy and O'Brien, 2010), or scaffolds with very large pore sizes where a flat morphology type dominates (Vance et al, 2005). Furthermore, assuming constant cell properties (e.g integrin density), bridged cells would be expected to have fewer integrin-matrix interactions as they have smaller surface areas of attachment, resulting in a reduced adhesive force.…”

Section: Introductionmentioning

confidence: 99%

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Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor

McCoy

Jungreuthmayer

O’Brien

2012

Biotech & Bioengineering

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FJ. Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor. Biotechnology and Bioengineering. 2012;109(6):1583-1594.-Use LicenceAttribution-Non-Commercial-ShareAlike 1.0 You are free:• to copy, distribute, display, and perform the work.• to make derivative works. Under the following conditions:• Attribution -You must give the original author credit.• Non-Commercial -You may not use this work for commercial purposes.• AbstractMechanically stimulating cell-seeded scaffolds by flow-perfusion is one approach utilised for developing clinically applicable bone graft substitutes. A key challenge is determining the magnitude of stimuli to apply that enhances cell differentiation but minimises cell detachment from the scaffold. In this study we employed a combined computational modelling and experimental approach to examine how the scaffold mean pore size influences cell attachment morphology and subsequently impacts upon cell deformation and detachment when subjected to fluid-flow. Cell detachment from osteoblast-seeded collagen-GAG scaffolds was evaluated experimentally across a range of scaffold pore sizes subjected to different flow-rates and exposure times in a perfusion bioreactor. Cell detachment was found to be proportional to flow-rate and inversely proportional to pore size. Using this data, a theoretical model was derived that accurately predicted cell detachment as a function of mean shear stress, mean pore size and time. Computational modelling of cell deformation in response to fluid flow showed the percentage of cells exceeding a critical threshold of deformation correlated with cell detachment experimentally and the majority of these cells were of a bridging morphology (cells stretched across pores). These findings will help researchers optimise the mean pore size of scaffolds and perfusion bioreactor operating conditions to manage cell detachment when mechanically simulating cells via flow perfusion.

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Bioreactors

Henstock

Haj

2016

Mechanobiology

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Influence of Shear Stress in Perfusion Bioreactor Cultures for the Development of Three-Dimensional Bone Tissue Constructs: A Review

Cited by 181 publications

References 135 publications

A simple rocker‐induced mechanical stimulus upregulates mineralization by human osteoprogenitor cells in fibrous scaffolds

A simple rocker‐induced mechanical stimulus upregulates mineralization by human osteoprogenitor cells in fibrous scaffolds

Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor

Bioreactors

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