Vocal Fold Tissue Repair<i>in Vivo</i>Using a Synthetic Extracellular Matrix

Duflo, S.; Thibeault, Susan L.; Li, Wenhua; Shu, Xiao Zheng; Prestwich, Glenn D.

doi:10.1089/ten.2006.12.2171

Cited by 156 publications

(138 citation statements)

References 47 publications

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“…Its preparation protocol is very "user-friendly" and suitable for large-scale experimental protocols, its gelation time can be adjusted by varying pH or temperature, and its compliance can be altered by adjusting the degree of cross-linking [44]. In addition, its nature overcomes the issue of immunogenicity in in vivo applications [27][28][29][30][31][32][33]. In this study, the cellular morphology in 3-D encapsulated Extracel ™ was mostly rounded rather than the stretched, spindle-shape appearance seen in other scaffolds.…”

Section: Discussionmentioning

confidence: 99%

“…Another ECM equivalent, Extracel ™ , consists of a chemically modified hyaluronan (CMHA-S, also known as Carbylan ™ -S) and gelatin (Gtn-DTPH), which are co-cross-linked with polyethylene glycol diacrylate (PEGDA) [24,25]. This synthetic ECM (sECM) has been used successfully in numerous tissue engineering applications, has broad applicability in drug discovery [26], and is suitable for both 3-D and pseudo-3-D plating [27][28][29][30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

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Effects of extracellular matrix analogues on primary human fibroblast behavior

2008

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In vitro cell culture is a vital research tool for cell biology, pharmacology, toxicology, protein production, systems biology and drug discovery. Traditional culturing methods on plastic surfaces do not accurately represent the in vivo environment, and a paradigm shift from two-dimensional to three-dimensional (3-D) experimental techniques is underway. To enable this change, a variety of natural, synthetic and semi-synthetic extracellular matrix (ECM) equivalents have been developed to provide an appropriate cellular microenvironment. We describe herein an investigation of the properties of four commercially available ECM equivalents on the growth and proliferation of primary human tracheal scar fibroblast behavior, both in 3-D and pseudo-3-D conditions. We also compare subcutaneous tissue growth of 3-D encapsulated fibroblasts in vivo in two of these materials, Matrigel ™ and Extracel ™ . The latter shows increased cell proliferation and remodeling of the ECM equivalent. The results provide researchers with a rational basis for selection of a given ECM equivalent based on its biological performance in vitro and in vivo, as well as the practicality of the experimental protocols. Biomaterials that use a customizable glycosaminoglycan-based hydrogel appear to offer the most convenient and flexible system for conducting in vitro research that accurately translates to in vivo physiology needed for tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of extracellular matrix analogues on primary human fibroblast behavior

2008

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“…In ideal cases, injectable biomaterials are used to regenerate the extracellular matrix (ECM) in the LP and to restore the viscoelastic functions of the damaged VF tissue. [2][3][4] One challenge in designing VF-specific biomaterials is that their long-term functional outcomes are complicated by the phonation-induced biomechanical stimulation. In addition to the cell-biomaterial interactions that are pertinent to the chemical properties of the biomaterials, biomechanical stimulation also affects cell functions in VF growth and regeneration.…”

Section: Introductionmentioning

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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“…28 The optimal sECM for both in vitro applications in 3D cell culture as well as in vivo applications in tissue repair has proven to be Carbylan TM -GSX 28 an sECM that is composed of thiolated gelatin and the thiolated biopolymer Carbylan TM -S. The efficacy of an injectable Carbylan TM -GSX hydrogel in restoring viscous and elastic moduli following scoop biopsy in rabbit vocal folds demonstrated that soft tissue repair was facilitated in vivo with this novel biomaterial. 29 We hypothesized that incorporation of growth factors and cytokines into Carbylan TM -GSX would further improve its tissue repair properties. We further hypothesized that this sECM could improve the rate and quality of repair in bone as well as in soft tissues.…”

Section: Introductionmentioning

confidence: 99%

Accelerated repair of cortical bone defects using a synthetic extracellular matrix to deliver human demineralized bone matrix

et al. 2006

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Injectable hydrogel and porous sponge formulations of Carbylan TM -GSX, a crosslinked synthetic extracellular matrix (ECM), were used to deliver human demineralized bone matrix (DBM) in a rat femoral defect model. A cortical, full-thickness 5-mm defect was created in two femurs of each rat. Six rats were assigned to each of five experimental groups (thus, 12 defects per group). The defects were either untreated or filled with Carbylan TM -GSX hydrogel or sponges with or without 20% (w/v) DBM. Radiographs were obtained on day 1 and at weeks 2, 4, 6, and 8 postsurgery of each femur. Animals were sacrificed at week 8 postsurgery and each femur was fixed, embedded, sectioned, and processed for Masson's Trichrome staining. The bone defects were measured from radiographs and the fraction of bone healing was calculated. The average fractions of bone healing for each group were statistically different among all groups, and all treatment groups were significantly better than the control group. The Carbylan TM -GSX sponge with DBM was superior to the sponge without DBM and to the hydrogel with DBM. Histology showed that defects treated with the Carbylan TM -GSX sponge plus DBM were completely filled with newly generated bone tissue with a thickness comparable to native bone. Carbylan TM -GSX sponge was an optimal delivery vehicle for human DBM to accelerate bone healing. ß

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Vocal Fold Tissue Repairin VivoUsing a Synthetic Extracellular Matrix

Cited by 156 publications

References 47 publications

Effects of extracellular matrix analogues on primary human fibroblast behavior

Effects of extracellular matrix analogues on primary human fibroblast behavior

A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications

Accelerated repair of cortical bone defects using a synthetic extracellular matrix to deliver human demineralized bone matrix

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