Vocal Fold Tissue Project :: The Center for Translational Cancer Research (CTCR) at the University of Delaware

Figure 1. H&E staining of a coronal section through a normal human vocal fold. 1: epithelium; 2: lamina propria; 3. vocalis muscle.

Vocal folds are located side by side in the larynx just above the trachea. In human, each fold is roughly 10-15 mm in length and 2-4 mm thick. Histologically, vocal fold is a laminated structure consisting of stratified squamous epithelium, lamina propria (LP) and vocalis muscle (Figure 1). A great variety of sounds are produced when the vocal folds are blown apart into entrained vibration by the tracheal air-stream. Under normal conditions, vocal folds can sustain up to 30% strain at frequencies of 75 to 1000 Hz. However, mechanical stresses from excessive phonation and deleterious environmental factors such as smoke, alcohol, radiation, and refluxed stomach acid can cause damage to this delicate system, resulting in basement-membrane-zone phonotrauma in the superficial lamina propria (SLP). This phonotrauma morphologically presents as nodules polyps, ectasias, varices and sulcus deformities at the medial surface of the vocal folds. The presence of scar tissue disrupts the natural pliability of the lamina propria and results in hoarseness and other symptoms of vocal dysfunction. More severe voice disorders result from chronic irritation such as cigarette smoke, giving rise to life-threatening laryngeal cancer. Unlike the benign lesions discussed above, laryngeal cancer not only invades the surface tissues, but also penetrates deep into the vocal fold body. Depending on the size, location, and time of cancer detection, one or more of the following approaches may be used: radiation therapy, chemotherapy and laryngectomy. In these cases, patients need a new way of breathing and a new sound source for speech.

Although a variety of techniques have been applied to treat voice disorders, successful treatment of voice disorder remains a significant therapeutic challenge. Tissue engineering methods hold great promise for the restoration of functional vocal folds. The development of advanced materials with appropriate organization and mechanical properties could therefore permit functional voice recovery as well as to provide an in vitro platform for the investigation of vocal fold diseases and discovery of new therapeutics.

Figure 2. Scanning electron micrograph of injectable hydrogel microspheres.

Two basic paradigms for vocal fold tissue engineering can be employed. The first method is based on a minimally invasive technique whereby smart, responsive and multifunctional biomaterials (Figure 2) are directly injected into the damaged vocal fold so as to afford in vivo engineering of vocal fold ECM. The second method relies on in vitro functional tissue formation by the appropriate combination of cells, artificial scaffolds (Figure 3), biological cues and mechanical stimulation. A combination of both approaches will likely be critical for addressing the significant challenges posed by the tissue engineering of functional vocal folds.

Figure 3. Scaffold used for in vitro tissue engineering of vocal fold.

We are closely collaborating with Dr. Steven M. Zeitels at the Center for Laryngeal Surgery & Voice Rehabilitation at Massachusetts General Hospital and Dr. Robert Witt at Christiana Care Hospital. The overall research program has a distinct multidisciplinary theme ranging from materials synthesis and biological characterization to tissue engineering. We strive to build a strong research program that not only educate students but also advances our understanding of life.