Medical Student Research Fellowship for Summer 2009

Mentor: Roger W. Chan, Ph.D., Associate Professor
Department: Otolaryngology-Head and Neck Surgery; Biomedical Engineering
Room number: G7.220A
Mail Code: 9035
Phone number: 214-648-0386
E-mail: roger.chan@utsouthwestern.edu
Project title: The use of bovine scaffolds for vocal fold reconstruction and remodeling in the rabbit model

Human subjects IRB approved project number (where applicable): not applicable

Animal subjects IRB approved project number (where applicable): 2009-0059

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) Basic research

Brief Description of Project:

Reconstruction of injured vocal fold tissue is a difficult task due to the unique multi-layered structure of the human vocal folds. A major line of current research focuses on the development of implantable materials with biomechanical and vibratory properties similar to native vocal fold mucosa so they can be used to replace missing vocal fold tissue and restore vibration for voice production. Our laboratory has developed a bovine acellular scaffold for vocal fold tissue regeneration (Xu et al., 2007, Tissue Engineering, 13, 551-566). The biocompatibility of this scaffold has been tested in a rat model of vocal fold injury in terms of in vivo host response, host tissue remodeling, and scaffold degradation. Current work extends the testing of the bovine scaffold to a rabbit model of vocal fold injury, as well as further characterization of the host cellular response in both the rat and rabbit models.

The student's role in this project will be the performance of immunohistochemical staining of harvested animal vocal fold tissues following implantation of the bovine acellular scaffold in vivo. Specific cell surface markers such as CD80, CD163, CD4+, CD8+, vimentin, and CD68 will be probed. The student will learn the techniques of immunohistochemistry. She will then carry out quantitative image analysis on the different cell types targeted by the markers. Through this project, the student will gain hands-on experience with a widely used technique in biomedical research, as well as in-depth knowledge on cellular inflammatory response, an area of emphasis covered in the medical school curriculum.

The student will also have the opportunity to participate in excised larynx phonation experiments, where excised animal larynges will be mounted on an artificial trachea delivering warmed and humidified air with precisely controlled airflow and pressure. The aerodynamic parameters under which artificial phonation is created provide insight into the biomechanical and vibratory properties of the vocal folds being tested. While the responsibility of these experiments lies with other lab personnel, the student can assist in the harvest and dissection of tissues as well as some experimental measurements in order to gain experience in a biomechanics-based research project in the Laryngeal Physiology and Biomechanics Laboratory.

Finally, for the student who has a strong clinical interest in voice disorders, we will build in times of observation in the UTSW Clinical Center for Voice Care, and/or observation of laryngeal surgeries with Ted Mau, M.D., Ph.D., Assistant Professor of Otolaryngology and Director of the Voice Center. This will provide the student with a continuum of experience from the bench to the bedside. Both immunohistochemistry and excised larynx phonation experiments lend themselves to flexible scheduling such that a small component of clinical observation can be easily built into the student's schedule to enhance her overall summer experience.

Previous Research Activities or Publications with Medical Students:

Guy Efune, M.D. (First year resident in Otolaryngology, UTSW) "Acellular scaffolds for vocal fold reconstruction in a rat model", Medical Student Research Project, UTSW (2007).

Lindsay Young, M.D. (Second year resident in Otolaryngology, UTSW) "Relative densities of collagen and elastin in the vocal fold lamina propria", Medical Student Research Project, UTSW (2005-2006).

Sean Callahan, M.D. (Second year resident in Otolaryngology, UTSW) "An analytical review of tensile stress-strain properties of human and animal vocal folds", Medical Student Research Project, UTSW (2005-2006).

Allis Cho, M.D. (Second year resident in Otolaryngology, LSU - Shreveport) "Viscoelastic shear properties of human and animal vocal folds", Medical Student Research Project, UTSW (2005-2006).

Publications:

Chan, R.W., Fu, M., Young, L., Tirunagari, N. (2007). Relative contributions of collagen and elastin to elasticity of the vocal fold under tension. Annals of Biomedical Engineering, 35, 1471-1483.

Xu, C.C., Chan, R.W., Weinberger, D.G., Efune, G., Pawlowski, K.S. (2009). A bovine acellular scaffold for vocal fold reconstruction in a rat model. Journal of Biomedical Materials Research Part A (in press).

Xu, C.C., Chan, R.W., Weinberger, D.G., Efune, G.., Pawlowski, K.S. (2009). Controlled-release of hepatocyte growth factor from a bovine acellular scaffold for vocal fold reconstruction. Journal of Biomedical Materials Research Part A (in review).