Design and validation of a bioreactor for engineering vocal fold tissues under combined tensile and vibrational stresses

Titze, Ingo R.; Hitchcock, Robert W.; Broadhead, Kelly; Webb, K. E.; Li, Wenhua; Gray, Steven D.; Tresco, Patrick A.

doi:10.1016/j.jbiomech.2004.01.007

Cited by 106 publications

(115 citation statements)

References 14 publications

(18 reference statements)

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…Obviously, the bioreactor used in the current investigation does not produce physiologically relevant forces making any definitive statements about the role of mechanical forces in vocal fold healing premature. To address this issue, Titze et al 30 recently described the development of a novel bioreactor approximating phonatory forces. However, this technology is not readily available at this time.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Biomechanical Strain Inhibits IL-1β–induced Inflammation in Vocal Fold Fibroblasts

et al. 2007

View full text Add to dashboard Cite

SummaryDespite the fact that vocal folds are subjected to extensive mechanical forces, the role of mechanical strain in vocal fold wound healing has been overlooked. Recent studies on other tissues have demonstrated that low physiological levels of mechanical forces are beneficial to injured tissues, reduce inflammation, and induce synthesis of matrix-associated proteins essential for enhanced wound healing. In this study, we speculated that mechanical strain of low magnitudes also attenuates the production of inflammatory mediators and alters the extracellular matrix synthesis to augment wound healing in cultured vocal fold fibroblasts. To test this hypothesis, fibroblasts from rabbit vocal folds were isolated and exposed to various magnitudes of cyclic tensile strain (CTS) in the presence or absence of interleukin-1β (IL-1β). Results suggest that IL-1β activates proinflammatory gene transcription in vocal fold fibroblasts. Furthermore, CTS abrogates the IL-1β-induced proinflammatory gene induction in a magnitude-dependent manner. In addition, CTS blocks IL-1β-mediated inhibition of collagen type I synthesis, and thereby upregulates collagen synthesis in the presence of IL-1β. These findings are the first to reveal the potential utility of low levels of mechanical signals in vocal fold wound healing, and support the emerging on vivo data suggesting beneficial effects of vocal exercise on acute phonotrauma.

show abstract

Section: Discussionmentioning

confidence: 99%

Dynamic Biomechanical Strain Inhibits IL-1β–induced Inflammation in Vocal Fold Fibroblasts

et al. 2007

View full text Add to dashboard Cite

show abstract

“…[9][10][11][12][13][14][15] The first mechanically driven VF bioreactor was designed to impose a 20% static axial strain and a 100 Hz vibratory stimulation for 6 h on human laryngeal fibroblasts seeded in threedimensional (3D) Tecoflex Ò porous substrates. 9 A modest increase in the cell density was observed along with slightly greater amounts of major ECM proteins in the stimulated samples than in the controls. Another mechanically driven bioreactor was developed to investigate the effects of high-frequency substrate vibratory stimulation at 100 Hz on human laryngeal fibroblasts seeded in 3D Tecoflex substrates.…”

Section: Fig 2 Computer-aided Design Drawings Of the Bioreactor (A)mentioning

confidence: 99%

“…No protein analysis at the ECM level was performed, and the stimulation frequency range was limited to 0.005 -0.5 Hz, which is much lower than the human phonation range. In another mechanically driven bioreactor, Titze et al's bioreactor concept 9 was revisited to incorporate a mechanism for VF collision. 13 The influence of vibratory stimulation, 20% axial strain, and VF collision on human VF fibroblasts and human bone marrow mesenchymal stem cells was investigated.…”

Section: Fig 2 Computer-aided Design Drawings Of the Bioreactor (A)mentioning

confidence: 99%

See 1 more Smart Citation

A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications

Latifi

Heris

Thomson

et al. 2016

Tissue Engineering Part C: Methods

View full text Add to dashboard Cite

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.

show abstract

“…One explanation could be that fibroblasts exposed to mechanical forces have stronger production of extracellular matrix constituents, including HA, than fibroblasts that are not exposed to mechanical forces, 18 and respiratory epithelium takes no part in voice production. However, small accumulations of HA between cylindrical cells could facilitate smaller changes in the shape of the epithelium.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan in Human Vocal Folds in Smokers and Nonsmokers—A Histochemical Study

et al. 2016

View full text Add to dashboard Cite

Summary Objectives/hypothesisTo study the hyaluronan occurrence in human vocal folds, with special regards to gender and smoking and to discuss the implications of findings. Study DesignThis is a descriptive/morphologic study. MethodsSixteen cadaveric vocal folds from eight individuals between 58 and 90 years old (six women and two men) were removed and studied morphologically. Three of the individuals had been cigarette smokers.A direct method for hyaluronan histochemistry using a hyaluronan-binding protein probe (HABP) was used to visualize the polysaccharide. Five examiners performed an analysis of the intensities of hyaluronan staining, independently. ResultsWe observed intense hyaluronan staining of the vocal folds of which those from women stained considerably stronger than those from men. Stratified squamous epithelium stained for hyaluronan in all sections, whereas respiratory epithelium only stained weakly or not at all. The highest accumulation of hyaluronan occurred subepithelially in the lamina propria, corresponding to Reinke's space. It was observed that vocal folds from smokers were more intensively stained than those from nonsmokers. 2 ConclusionsHyaluronan is found in all layers of the human vocal fold. Contradictory to earlier studies, hyaluronan was visualized in squamous epithelium, where it may function as an impact protector. The occurrence of hyaluronan in smokers may have implications in the development of vocal fold inflammation and tumor initiation as hyaluronan is an important molecule in these processes.

show abstract

Design and validation of a bioreactor for engineering vocal fold tissues under combined tensile and vibrational stresses

Cited by 106 publications

References 14 publications

Dynamic Biomechanical Strain Inhibits IL-1β–induced Inflammation in Vocal Fold Fibroblasts

Dynamic Biomechanical Strain Inhibits IL-1β–induced Inflammation in Vocal Fold Fibroblasts

A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications

Hyaluronan in Human Vocal Folds in Smokers and Nonsmokers—A Histochemical Study

Contact Info

Product

Resources

About