A bioreactor system for in vitro tendon differentiation and tendon tissue engineering

Youngstrom, Daniel W.; Rajpar, Ibtesam; Kaplan, David L.; Barrett, Jennifer G.

doi:10.1002/jor.22848

Cited by 77 publications

(81 citation statements)

References 45 publications

(81 reference statements)

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“…Here, mechanical stimulation was performed over 8 or 10 days until samples were harvested; hence, the results of the present study add to these published data very well. Youngstrom et al found increased gene expression levels of scleraxis, collagen 1, and decorin but decreased expression of collagen 3 when using a stimulation regime with 3% strain, being accompanied by improved biomechanical properties [39]. Considering Youngstrom et al's and our findings at the same time, it can be assumed that scleraxis and decorin expression levels not only are elevated very early but can be maintained in the model system used.…”

Section: Discussionsupporting

confidence: 70%

“…Intriguingly, studies using an approach very similar to the current one, combining cell culture on decellularized tendon scaffolds and mechanical stimulation, were published recently [39, 43]. Here, mechanical stimulation was performed over 8 or 10 days until samples were harvested; hence, the results of the present study add to these published data very well.…”

Section: Discussionmentioning

confidence: 56%

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Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short‐Term Cyclic Stretching

Burk

Plenge

Brehm

et al. 2016

Stem Cells International

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Tendon and ligament pathologies are still a therapeutic challenge, due to the difficulty in restoring the complex extracellular matrix architecture and biomechanical strength. While progress is being made in cell-based therapies and tissue engineering approaches, comprehensive understanding of the fate of progenitor cells in tendon healing is still lacking. The aim of this study was to investigate the effect of decellularized tendon matrix and moderate cyclic stretching as natural stimuli which could potentially direct tenogenic fate. Equine adipose-derived mesenchymal stromal cells (MSC) were seeded on decellularized tendon matrix scaffolds. Mechanical stimulation was applied in a custom-made cyclic strain bioreactor. Assessment was performed 4 h, 8 h, and 24 h following mechanical stimulation. Scaffold culture induced cell alignment and changes in expression of tendon-related genes, although cell viability was decreased compared to monolayer culture. Short mechanical stimulation periods enhanced most of the scaffold-induced effects. Collagen 1A2 expression levels were decreased, while collagen 3A1 and decorin levels were increased. Tenascin-C and scleraxis expression showed an initial decrease but had increased 24 h after stimulation. The results obtained suggest that decellularized tendon matrix, supported by cyclic stretching, can induce tenogenic differentiation and the synthesis of tendon components important for matrix remodeling.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 56%

Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short‐Term Cyclic Stretching

Burk

Plenge

Brehm

et al. 2016

Stem Cells International

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“…When canine ASCs were grown in 3D culture in a collagen and human tendon ECM composite hydrogel with static tension, the cells underwent differentiation towards tenocytes and showed increased alignment and tenomodulin expression [44]. One group observed improved horse MSC integration and differentiation into thick horse tendon ECM sections with 3% strain compared to lesser values [26]. To increase tendon-like architecture of the material, one study took canine MSC-seeded tendon sections and sutured them together to create bundles that were cultured in suspension.…”

Section: Ecm Effects On Cell Differentiationmentioning

confidence: 99%

Controlling stem cell behavior with decellularized extracellular matrix scaffolds

Agmon

Christman

2016

Current Opinion in Solid State and Materials Science

150

104

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Decellularized tissues have become a common regenerative medicine platform with multiple materials being researched in academic laboratories, tested in animal studies, and used clinically. Ideally, when a tissue is decellularized the native cell niche is maintained with many of the structural and biochemical cues that naturally interact with the cells of that particular tissue. This makes decellularized tissue materials an excellent platform for providing cells with the signals needed to initiate and maintain differentiation into tissue-specific lineages. The extracellular matrix (ECM) that remains after the decellularization process contains the components of a tissue specific microenvironment that is not possible to create synthetically. The ECM of each tissue has a different composition and structure and therefore has unique properties and potential for affecting cell behavior. This review describes the common methods for preparing decellularized tissue materials and the effects that decellularized materials from different tissues have on cell phenotype.

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“…The bioreactor was first operated without phonatory stimulation for a duration of 3 days. 9,15,27,28 Subsequently, the bioreactor was phonated for 2 h each day over a period of 4 days. The bioreactor was phonated for 1 h, rested for 15 min, and phonated for another hour.…”

Section: Phonatory Stimulationmentioning

confidence: 99%

A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications

Latifi

Heris

Thomson

et al. 2016

Tissue Engineering Part C: Methods

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The human vocal folds (VFs) undergo complex biomechanical stimulation during phonation. The aim of the present study was to develop and validate a phono-mimetic VF flow perfusion bioreactor, which mimics the mechanical microenvironment of the human VFs in vitro. The bioreactor uses airflow-induced self-oscillations, which have been shown to produce mechanical loading and contact forces that are representative of human phonation. The bioreactor consisted of two synthetic VF replicas within a silicone body. A cell-scaffold mixture (CSM) consisting of human VF fibroblasts, hyaluronic acid, gelatin, and a polyethylene glycol cross-linker was injected into cavities within the replicas. Cell culture medium (CCM) was perfused through the scaffold by using a customized secondary flow loop. After the injection, the bioreactor was operated with no stimulation over a 3-day period to allow for cell adaptation. Phonation was subsequently induced by using a variable speed centrifugal blower for 2 h each day over a period of 4 days. A similar bioreactor without biomechanical stimulation was used as the nonphonatory control. The CSM was harvested from both VF replicas 7 days after the injection. The results confirmed that the phono-mimetic bioreactor supports cell viability and extracellular matrix proteins synthesis, as expected. Many scaffold materials were found to degrade because of challenges from phonation-induced biomechanical stimulation as well as due to biochemical reactions with the CCM. The bioreactor concept enables future investigations of the effects of different phonatory characteristics, that is, voice regimes, on the behavior of the human VF cells. It will also help study the long-term functional outcomes of the VF-specific biomaterials before animal and clinical studies.

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A bioreactor system for in vitro tendon differentiation and tendon tissue engineering

Cited by 77 publications

References 45 publications

Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short‐Term Cyclic Stretching

Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short‐Term Cyclic Stretching

Controlling stem cell behavior with decellularized extracellular matrix scaffolds

A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications

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