Bioreactors for bone tissue engineering

Haj, Alicia J. El; Cartmell, Sarah H.

doi:10.1243/09544119jeim802

Cited by 38 publications

(38 citation statements)

References 35 publications

(43 reference statements)

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“…Different bioreactor systems have been designed and used for the cultivation of bone-engineered substitutes, including spinner flasks, and rotating vessels, perfusion and compression systems, each providing specific mechanical stresses and regimes for the proper stimulation of the cell/scaffold constructs (for a review see Ref. 4 ).…”

Section: Introductionmentioning

confidence: 99%

Human Embryonic Stem Cell-Derived Mesodermal Progenitors Display Substantially Increased Tissue Formation Compared to Human Mesenchymal Stem Cells Under Dynamic Culture Conditions in a Packed Bed/Column Bioreactor

Peppo

Sladkova

Sjövall

et al. 2013

Tissue Engineering Part A

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Bone tissue engineering represents a promising strategy to obviate bone deficiencies, allowing the ex vivo construction of bone substitutes with unprecedented potential in the clinical practice. Considering that in the human body cells are constantly stimulated by chemical and mechanical stimuli, the use of bioreactor is emerging as an essential factor for providing the proper environment for the reproducible and large-scale production of the engineered substitutes. Human mesenchymal stem cells (hMSCs) are experimentally relevant cells but, regardless the encouraging results reported after culture under dynamic conditions in bioreactors, show important limitations for tissue engineering applications, especially considering their limited proliferative potential, loss of functionality following protracted expansion, and decline in cellular fitness associated with aging. On the other hand, we previously demonstrated that human embryonic stem cell-derived mesodermal progenitors (hES-MPs) hold great potential to provide a homogenous and unlimited source of cells for bone engineering applications. Based on prior scientific evidence using different types of stem cells, in the present study we hypothesized that dynamic culture of hES-MPs in a packed bed/column bioreactor had the potential to affect proliferation, expression of genes involved in osteogenic differentiation, and matrix mineralization, therefore resulting in increased bone-like tissue formation. The reported findings suggest that hES-MPs constitute a suitable alternative cell source to hMSCs and hold great potential for the construction of bone substitutes for tissue engineering applications in clinical settings.

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Section: Introductionmentioning

confidence: 99%

Human Embryonic Stem Cell-Derived Mesodermal Progenitors Display Substantially Increased Tissue Formation Compared to Human Mesenchymal Stem Cells Under Dynamic Culture Conditions in a Packed Bed/Column Bioreactor

Peppo

Sladkova

Sjövall

et al. 2013

Tissue Engineering Part A

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“…[1][2][3] Numerous bioreactors have been developed to provide physical forces such as hydrostatic pressure. Hydrostatic pressure has been shown to be an important mechanical stimulus for the direction of cell fate in various tissues, including articular cartilage, the intervertebral disc, bone, and the vascular system.…”

mentioning

confidence: 99%

Evaluation of the Growth Environment of a Hydrostatic Force Bioreactor for Preconditioning of Tissue-Engineered Constructs

Reinwald

Leonard²,

Henstock³

et al. 2015

Tissue Engineering Part C: Methods

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Bioreactors have been widely acknowledged as valuable tools to provide a growth environment for engineering tissues and to investigate the effect of physical forces on cells and cell-scaffold constructs. However, evaluation of the bioreactor environment during culture is critical to defining outcomes. In this study, the performance of a hydrostatic force bioreactor was examined by experimental measurements of changes in dissolved oxygen (O 2 ), carbon dioxide (CO 2 ), and pH after mechanical stimulation and the determination of physical forces (pressure and stress) in the bioreactor through mathematical modeling and numerical simulation. To determine the effect of hydrostatic pressure on bone formation, chick femur skeletal cell-seeded hydrogels were subjected to cyclic hydrostatic pressure at 0-270 kPa and 1 Hz for 1 h daily (5 days per week) over a period of 14 days. At the start of mechanical stimulation, dissolved O 2 and CO 2 in the medium increased and the pH of the medium decreased, but remained within human physiological ranges. Changes in physiological parameters (O 2 , CO 2 , and pH) were reversible when medium samples were placed in a standard cell culture incubator. In addition, computational modeling showed that the distribution and magnitude of physical forces depends on the shape and position of the cell-hydrogel constructs in the tissue culture format. Finally, hydrostatic pressure was seen to enhance mineralization of chick femur skeletal cell-seeded hydrogels.

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“…1,2,4,6,27,28 Constructs cultured in perfusion bioreactors have frequently been demonstrated to produce bone subcutaneously 9,10,29 and evidence of perfusion cultured constructs enhancing bone repair exists; …”

Section: Discussionmentioning

confidence: 99%

In VivoBone Regeneration Using Tubular Perfusion System Bioreactor Cultured Nanofibrous Scaffolds

Yeatts

Both

Yang

et al. 2014

Tissue Engineering Part A

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Bioreactors for bone tissue engineering

Cited by 38 publications

References 35 publications

Human Embryonic Stem Cell-Derived Mesodermal Progenitors Display Substantially Increased Tissue Formation Compared to Human Mesenchymal Stem Cells Under Dynamic Culture Conditions in a Packed Bed/Column Bioreactor

Human Embryonic Stem Cell-Derived Mesodermal Progenitors Display Substantially Increased Tissue Formation Compared to Human Mesenchymal Stem Cells Under Dynamic Culture Conditions in a Packed Bed/Column Bioreactor

Evaluation of the Growth Environment of a Hydrostatic Force Bioreactor for Preconditioning of Tissue-Engineered Constructs

In VivoBone Regeneration Using Tubular Perfusion System Bioreactor Cultured Nanofibrous Scaffolds

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