We evaluated cross-linked hyaluronic acid (hylan B gel) as a scaffold for tissue regeneration and mucosal wave restoration in carbon dioxide laser-ablated canine vocal folds.
Five beagles underwent stroboscopy before ablation of the left vocal fold with a carbon dioxide laser. Four weeks later, stroboscopy was repeated before and after submucosal injection of hylan B gel into the left vocal fold of 4 animals and of saline solution in 1 animal. Stroboscopy was repeated 12 weeks later, and histologic analysis was performed.
Four weeks after laser ablation, all animals had soft tissue defects and absence of mucosal waves. Hylan B injection restored mucosal waves, and saline injection did not. Twelve weeks after injection, hylan B-injected larynges had tissue regeneration and mucosal waves, and the saline-injected larynx had neither. Histology showed regenerated lamina propria with residual foci of hylan B in the hylan B-injected larynges and dense submucosal scar in the saline-injected animal.
Submucosal hylan B gel injection in laser-ablated canine vocal folds restored tissue volume and mucosal waves and facilitated functional tissue regeneration over 12 weeks. Hylan B gel may have utility as a soft tissue scaffold for rehabilitation of phonatory function in vocal folds with lamina propria defects.
"Mechanical stress from excessive phonation, deleterious environmental factors, and pathological conditions can disrupt the natural pliability of the vocal folds, resulting in a wide spectrum of vocal disorders and causing significant implications for individual health, social productivity, and occupational function (Zeitels et al., 2002). Surgical approaches for vocal fold augmentation or mucosal reconstruction have employed a variety of either injectable or implantable synthetic and biological materials (Hallén et al., 2001; Hirano et al., 2008; Jahan-Parwar et al., 2008; Kwon and Lee, 2008; Kishirnoto et al., 2009; Kutty and Webb, 2009b). Although improvements in voice production have been reported, limitations such as implant migration, foreign body reaction, stiffness, immunological consequences, and the need of multi-stage procedures largely have prevented restoration of functional vocal fold tissue. "
[Show abstract][Hide abstract] ABSTRACT: The outstanding high-frequency properties of emerging resilin-like polypeptides (RLPs) have motivated their development for vocal fold tissue regeneration and other applications. Recombinant RLP hydrogels show efficient gelation, tunable mechanical properties, and display excellent extensibility, but little has been reported about their transient mechanical properties. In this manuscript, we describe the transient mechanical behavior of new RLP hydrogels investigated via both sinusoidal oscillatory shear deformation and uniaxial tensile testing. Oscillatory stress relaxation and creep experiments confirm that RLP-based hydrogels display significantly reduced stress relaxation and improved strain recovery compared to PEG-based control hydrogels. Uniaxial tensile testing confirms the negligible hysteresis, reversible elasticity and superior resilience (up to 98%) of hydrated RLP hydrogels, with Young's modulus values that compare favorably with those previously reported for resilin and that mimic the tensile properties of the vocal fold ligament at low strain (<15%). These studies expand our understanding of the properties of these RLP materials under a variety of conditions, and confirm the unique applicability, for mechanically demanding tissue engineering applications, of a range of RLP hydrogels.
Frontiers in Chemistry 04/2014; 2:21. DOI:10.3389/fchem.2014.00021
[Show abstract][Hide abstract] ABSTRACT: One potential treatment option for severe vocal fold scarring is to replace the vocal fold cover layer with a tissue-engineered structure containing autologous cells. As a first step toward that goal, we sought to develop a three-dimensional cell-populated matrix resembling the vocal fold layers of lamina propria and epithelium.
Basic science investigation.
Adipose-derived stem cells were cultured in fibrin hydrogels with various growth factors. At the end of the culture period, matrices were sectioned and labeled with immunomarkers to identify cell phenotype.
Adipose-derived stem cells survived, attached, and populated three-dimensional fibrin matrices. Under select conditions, a superficial layer of cells expressing epithelial marker proteins overlay a deeper mesenchymal cell layer.
A three-dimensional structure of fibrin and adipose-derived stem cells was created as a prototype vocal fold replacement. Two segregated cell phenotypes occurred, producing a bilayered structure resembling epithelium over lamina propria. This preliminary work demonstrates the feasibility of tissue engineering to produce structures for vocal fold replacement.
The Laryngoscope 01/2009; 120(1):125-31. DOI:10.1002/lary.20719 · 2.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Viscoelastic properties of numerous vocal fold injectables have been reported but not at speaking frequencies. For materials intended for Reinke's space, ramifications of property values are of great concern because of their impact on ease of voice onset. Our objectives were: 1) to measure viscoelastic properties of a new nonresorbing carbomer and well-known vocal fold injectables at vocalization frequencies using established and new instrumentation, and 2) to predict phonation threshold pressures using a computer model with intended placement in Reinke's space.
Rheology and phonation threshold pressure calculations.
Injectables were evaluated with a traditional rotational rheometer and a new piezo-rotary vibrator. Using these data at vocalization frequencies, phonation threshold pressures (PTP) were calculated for each biomaterial, assuming a low dimensional model with supraglottic coupling and adjusted vocal fold length and thickness at each frequency. Results were normalized to a nominal PTP value.
Viscoelastic data were acquired at vocalization frequencies as high as 363 to 1,400 Hz for six new carbomer hydrogels, Hylan B, and Extracel intended for vocal fold Reinke's space injection and for Cymetra (lateral injection). Reliability was confirmed with good data overlap when measuring with either rheometer. PTP predictions ranged from 0.001 to 16 times the nominal PTP value of 0.283 kPa.
Accurate viscoelastic measurements of vocal fold injectables are now possible at physiologic frequencies. Hylan B, Extracel, and the new carbomer hydrogels should generate easy vocal onset and sustainable vocalization based on their rheologic properties if injected into Reinke's space. Applications may vary depending on desired longevity of implant. Laryngoscope, 2010
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