Chet C. Xu

A bovine acellular scaffold for vocal fold reconstruction in a rat model

With a rat model of vocal fold injury, this study examined the in vivo host response to an acellular xenogeneic scaffold derived from the bovine vocal fold lamina propria, and the potential of the scaffold for constructive tissue remodeling. Bilateral wounds were created in the posterior vocal folds of 20 rats, and bovine acellular scaffolds were implanted into the wounds unilaterally, with the contralateral vocal folds as control. The rats were humanely sacrificed after 3 days, 7 days, 1 month, and 3 months, and the coronal sections of their larynges were examined histologically. Expressions of key matrix proteins including collagen I, collagen III, elastin, fibronectin, hyaluronic acid, and glycosaminoglycans (GAGs) were quantified with digital image analysis. Significant infiltration of host inflammatory cells and host fibroblasts in the scaffold implant was observed in the acute stage of wound repair (3 days and 7 days postsurgery). The mean relative densities of collagen I, collagen III, and GAGs in the implanted vocal folds were significantly higher than those in the control after 3 days, followed by gradual decreases over 3 months. Histological results showed that the scaffolds were apparently degraded by 3 months, with no fibrotic tissue formation or calcification. These preliminary findings suggested that the bovine acellular scaffold could be a potential xenograft for vocal fold regeneration.

Controlled release of hepatocyte growth factor from a bovine acellular scaffold for vocal fold reconstruction

A bovine acellular scaffold was found to facilitate tissue remodeling in a rat model of vocal fold injury, whereas hepatocyte growth factor (HGF) has been shown to have an antiscarring effect in the larynx. This study examined the loading and release kinetics of HGF in vitro, and the potential of the acellular scaffold as a timed-release system for the delivery of HGF in vivo. Bilateral wounds were created in the posterior vocal folds of 20 rats, with HGF-loaded acellular scaffolds implanted into the wounds unilaterally, and scaffolds without HGF implanted into the contralateral vocal folds as control. The rats were humanely sacrificed after 3, 7, 30, and 90 days and their larynges were examined histologically and immunohistochemically. Expressions of key matrix proteins in the vocal fold coronal sections were quantified by digital image analysis. Results demonstrated a gradual, sustained release of HGF for at least 7 days in vitro, consistent with the detection of glycosaminoglycans inherent of the scaffold. In rat vocal folds implanted with HGF-loaded scaffolds, apparently fewer inflammatory cells were observed 3 days after surgery when compared to the control. The mean relative densities of collagen III and hyaluronic acid were significantly lower than those of the control 7 days after surgery. Scaffold implants were apparently degraded by 3 months in all animals, with no evidence of fibrosis or calcification. These data suggested that the bovine acellular scaffold could be promising for the exogenous delivery of select growth factors in vivo.

Pore architecture of a bovine acellular vocal fold scaffold.

An acellular xenogeneic scaffold derived from the bovine vocal fold lamina propria has shown some promise for in vitro vocal fold tissue engineering. To further explore the potential of the scaffold for cellular attachment, migration, and infiltration, as well as the transport of oxygen, proteins, and nutrients in vivo, this study examined the architecture of pores in the scaffold in terms of several key parameters. Porosity was determined using a standard fluid replacement method with a pycnometer. Average pore size and the pore size distribution were assessed using digital image analysis of scanning electron micrographs. The intrinsic permeability to water was measured using a custom-built hydrostatic pressure apparatus as an estimation of the overall porous nature of the acellular scaffold. The results indicated that the bovine acellular scaffold has a reasonably high porosity (90.49 +/- 4.33%), a proper pore size distribution (>60% of the pores with equivalent diameters > or =10 microm and < 100 microm) that could facilitate cellular attachment and infiltration, as well as a relatively high intrinsic permeability (0.21-3.21 darcy) for the transport of soluble factors. These findings offered preliminary support of the potential of the scaffold for facilitating functional extracellular matrix remodeling in vocal fold reconstruction.

A rabbit vocal fold laser scarring model for testing lamina propria tissue‐engineering therapies

To develop a vocal fold scarring model using an ablative laser in the rabbit as a platform for testing bioengineered therapies for missing or damaged lamina propria.

A mixed-effects model approach for the statistical analysis of vocal fold viscoelastic shear properties

A mixed-effects model approach was introduced in this study for the statistical analysis of rheological data of vocal fold tissues, in order to account for the data correlation caused by multiple measurements of each tissue sample across the test frequency range. Such data correlation had often been overlooked in previous studies in the past decades. The viscoelastic shear properties of the vocal fold lamina propria of two commonly used laryngeal research animal species (i.e. rabbit, porcine) were measured by a linear, controlled-strain simple-shear rheometer. Along with published canine and human rheological data, the vocal fold viscoelastic shear moduli of these animal species were compared to those of human over a frequency range of 1-250Hz using the mixed-effects models. Our results indicated that tissues of the rabbit, canine and porcine vocal fold lamina propria were significantly stiffer and more viscous than those of human. Mixed-effects models were shown to be able to more accurately analyze rheological data generated from repeated measurements.

Pressure sensing using low-cost microstrip antenna sensor

This paper presents a novel pressure sensor consisting of a low-cost microstrip patch antenna placed a distance from a metal reflection plate. The pressure applied on the plate changes the distance between the metal plate and the patch antenna, which shifts the resonant frequency of the antenna sensor. The operation principle of the pressure sensor is firstly presented. Subsequently, the design and fabrication of the antenna sensor as well as the electromagnetic (EM) simulations of its response to the applied pressure are described. Finally, static experiments are performed to validate the performance of the pressure sensor and the results are discussed.

An investigation of left-right vocal fold symmetry in rheological and histological properties: Left-Right Vocal Fold Symmetry

The primary objective was to investigate the left–right vocal fold symmetry in rheological and histological properties using a rabbit model. The other objective was to develop statistical models for the comparison of rheological properties between paired vocal folds.

Corrigendum to “A mixed-effects model approach for the statistical analysis of vocal fold viscoelastic shear properties” [J. Mech. Behav. Biomed. Mater. 75 (2017) 477–485] (S1751616117303375) (10.1016/j.jmbbm.2017.08.006))

a Department of Otolaryngology-Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA Graduate Program in Biomedical Engineering, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA c Department of Speech Language Pathology, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan d Department of Quantitative Health Sciences, the Cleveland Clinic Foundation, Cleveland, OH 44195, USA e Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH 44106, USA Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

Design of a MRI-visible and radiopaque drug delivery coating for bioresorbable stents

Cardiovascular stents are currently being used for intraluminal stenting of the trachea for tracheomalacia treatment. These devices composed of permanent materials are controversial due to their limitations at internal reinforcement and biocompatibility, especially in pediatrics. We show in a pediatric tracheomalacia rabbit model, a poly-L-lactic acid (PLLA) Double Opposed Helical bioresorbable stent (DH) elicits a more mild inflammatory response in the malacic airway compared to a control metal stent. To further improve efficacy, a multi-drug delivery, bioresorbable coating was designed. The coating design controllably delivers ciprofloxacin (antibiotic) for one week and dexamethasone (anti-inflammatory agent) for three months. The bioresorbable polymeric components also demonstrate feasible visibility utilizing Magnetic Resonance Imaging (MRI). The local multi-drug delivery and imaging capabilities in this coating design in combination with the bioresorbable DH stent will result in a successful intervention specifically design for pediatric tracheomalacia. This design will eliminate long-term risks associated with current permanent devices and provide necessary theranostic agents to facilitate healing and monitor progress via non-invasive imaging techniques.Copyright