Indirect Low-Intensity Ultrasonic Stimulation for Tissue Engineering

Low-intensity ultrasound (LIUS) treatment has been shown to increase mass transport, which could benefit tissue grafts during the immediate postimplant period, when blood supply to the implanted tissue is suboptimal. In this in vitro study, we investigated effects of LIUS stimulation on dye diffusion, proliferation, metabolism, and tropomyosin expression of muscle cells (C2C12) and on tissue viability and gene expression of human adipose tissue organoids. We found that LIUS increased dye diffusion within adjacent tissue culture wells and caused anisotropic diffusion patterns. This effect was confirmed by a hydrophone measurement resulting in acoustic pressure 150–341 Pa in wells. Cellular studies showed that LIUS significantly increased proliferation, metabolic activity, and expression of tropomyosin. Adipose tissue treated with LIUS showed significantly increased metabolic activity and the cells had similar morphology to normal unilocular adipocytes. Gene analysis showed that tumor necrosis factor-alpha expression (a marker for tissue damage) was significantly lower for stimulated organoids than for control groups. Our data suggests that LIUS could be a useful modality for improving graft survival in vivo

Direct measurement and modeling of intraglottal, subglottal, and vocal fold collision pressures during phonation in an individual with a hemilaryngectomy

The purpose of this paper is to report on the first in vivo application of a recently developed transoral, dual-sensor pressure probe that directly measures intraglottal, subglottal, and vocal fold collision pressures during phonation. Synchronous measurement of intraglottal and subglottal pressures was accomplished using two miniature pressure sensors mounted on the end of the probe and inserted transorally in a 78-year-old male who had previously undergone surgical removal of his right vocal fold for treatment of laryngeal cancer. The endoscopist used one hand to position the custom probe against the surgically medialized scar band that replaced the right vocal fold and used the other hand to position a transoral endoscope to record laryngeal high-speed videoendoscopy of the vibrating left vocal fold contacting the pressure probe. Visualization of the larynx during sustained phonation allowed the endoscopist to place the dual-sensor pressure probe such that the proximal sensor was positioned intraglottally and the distal sensor subglottally. The proximal pressure sensor was verified to be in the strike zone of vocal fold collision during phonation when the intraglottal pressure signal exhibited three characteristics: an impulsive peak at the start of the closed phase, a rounded peak during the open phase, and a minimum value around zero immediately preceding the impulsive peak of the subsequent phonatory cycle. Numerical voice production modeling was applied to validate model-based predictions of vocal fold collision pressure using kinematic vocal fold measures. The results successfully demonstrated feasibility of in vivo measurement of vocal fold collision pressure in an individual with a hemilaryngectomy, motivating ongoing data collection that is designed to aid in the development of vocal dose measures that incorporate vocal fold impact collision and stresses.Fil: Mehta, Daryush D.. Massachusetts General Hospital; Estados UnidosFil: Kobler, James B.. Massachusetts General Hospital; Estados UnidosFil: Zeitels, Steven M.. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados UnidosFil: Zañartu, Matías. Universidad Técnica Federico Santa María; ChileFil: Ibarra, Emiro J.. Universidad Técnica Federico Santa María; ChileFil: Alzamendi, Gabriel Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Manriquez, Rodrigo. Universidad Técnica Federico Santa María; ChileFil: Erath, Byron D.. Clarkson University; Estados UnidosFil: Peterson, Sean D.. University of Waterloo; CanadáFil: Petrillo, Robert H.. Center For Laryngeal Surgery and Voice Rehabilitation; Estados UnidosFil: Hillman, Robert E.. Center For Laryngeal Surgery and Voice Rehabilitation; Estados Unidos. Harvard Medical School. Department of Medicine. Massachusetts General Hospital; Estados Unido

Injectable hyaluronic acid-dextran hydrogels and effects of implantation in ferret vocal fold

Injectable hydrogels may potentially be used for augmentation/regeneration of the lamina propria of vocal fold tissue. In this study, hyaluronic acid (HA) and dextran were chemically modified and subsequently crosslinked via formation of hydrazone bonds in phosphate buffer. Swelling ratios, degradation, and compressive moduli of the resulting hydrogels were investigated. It was found that the properties of HA-dextran hydrogels were variable and the trend of variation could be correlated with the hydrogel composition. The biocompatibility of three injectable HA-dextran hydrogels with different crosslinking density was assessed in the vocal fold region using a ferret model. It was found that HA-dextran hydrogels implanted for three weeks stimulated mild foreignbody reactions. Distinct tissue-material interactions were also observed for hydrogels made from different formulations: the hydrogel with the lowest crosslinking density was completely degraded in vivo; while material residues were visible for other types of hydrogel injections, with or without cell penetration into the implantation depending on the hydrogel composition. The in vivo results suggest that the HA-dextran hydrogel matrices can be further developed for applications of vocal fold tissue restoration. © 2010 Wiley Periodicals, Inc

Systems, devices and methods for imaging and surgery

Provided herein are devices, systems and methods for treating a vocal fold pathology by forming a substantially planar void below the epithelium of the vocal fold using optical energy. Also provided are devices, systems, and methods for combined imaging and treating of a vocal fold pathology.Board of Regents, University of Texas Syste

Polarization-Sensitive Optical Coherence Tomography Imaging of Benign and Malignant Laryngeal Lesions: An In Vivo Study

Objective. Optical coherence tomography (OCT), an imaging technology that provides cross-sectional subsurface tissue structure images using back-scattered light, is a promising noninvasive imaging modality for in vivo assessment of vocal fold layered microstructure. Polarization-sensitive OCT (PS-OCT) augments conventional OCT by detecting changes in the polarization state of reflected light. This study imaged various benign and malignant laryngeal pathologies in patients undergoing direct laryngoscopy under general anesthesia to determine whether PS-OCT would provide useful additional information about vocal fold microstructure and glottic surface pathology. Study Design. Prospective clinical trial. Setting. Tertiary care center. Subjects and Methods. Twenty-three patients who were undergoing microlaryngoscopy under general anesthesia for benign (n = 18) and malignant (n = 5) glottic disease were imaged bilaterally with OCT and PS-OCT (n = 46 vocal folds). Intraoperative microphotography guided placement of the imaging probe. Normal-appearing glottic tissue was also imaged if present. When clinically indicated, biopsy or complete removal of the lesion established histologic confirmation. Results. PS-OCT provided high-quality, vertical, cross-sectional images up to 1.2-mm deep that complemented microlaryngoscopy and conventional OCT for vocal fold pathologies. Scar tissue was visualized by PS-OCT, characterized by a birefringence pattern more intense than that of normal glottic tissue. Cancer typically showed disruption or absence of both layered structure and birefringence. Conclusion. Combining PS-OCT with OCT during human vocal cord imaging provides useful information in characterizing vocal cord lesions, particularly scar tissue. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2011

Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications

Particle size, stiffness and surface functionality are important in determining the injection site, safety and efficacy of injectable soft-tissue fillers. Methods to produce soft injectable biomaterials with controlled particle characteristics are therefore desirable. Here we report a method based on suspension photopolymerization and semi-interpenetrating network (semi-IPN) to synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of independently tunable size and stiffness. MP were prepared using acrylated forms of polyethylene glycol (PEG), gelatin and hyaluronic acid. Semi-IPN MP of PEG-diacrylate and PEG were used to study the effect of process parameters on particle characteristics. The process parameters were systematically varied to produce MP with size ranging from 115 to 515 μm and stiffness ranging from 190 to 1600 Pa. In vitro studies showed that the MP thus prepared were cytocompatible. The ratio and identity of the polymers used to make the semi-IPN MP were varied to control their stiffness and to introduce amine groups for potential functionalization. Slow-release polymeric particles loaded with Rhodamine or dexamethasone were incorporated in the MP as a proof-of-principle of drug incorporation and release from the MP. This work has implications in preparing injectable biomaterials of natural or synthetic polymers for applications as soft-tissue fillers. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved