PROJECT SUMMARY/ABSTRACT This research addresses an important public health concern, the development and maintenance of adequate pitch variation and vocal clarity throughout the life span. Evidence has been growing that vocal pitch range and stability of vocalization can be maintained with voice training and therapy techniques that rely heavily on repeated pitch glides, presumably to stretch the vocal ligament. It is impossible to measure directly the time-course of remodeling the vocal ligament with exercise in live humans. However, strong inferences can be drawn from structural and mechanical diversity across several species, from tissue engineering, and from computational modeling. In this proposal, we combine (1) microscopic imaging to test collagen density and fiber orientation in multiple species, (2) bioreactor design of a vocal ligament with combined axial and vibrational stress and selected growth factors, (3) finite-element computer modeling to predict fundamental frequency ranges and stability in vocal fold adduction, and (4) human subject exercise protocols to increase fundamental frequency range and vocal adduction control. While the aims can all be executed independently, they cross-validate each other on the basic premise that the vocal ligament is critical for fo range and can change over time. A first hypothesis is that the ligament can sustain high tension (up to 1 MPa) for high fundamental frequencies. A second hypothesis is that the vocal ligament serves as a stabilizer in vocal fold posturing and maintaining a consistently straight fold edge for glottal closure. Doses of repeated stretching are designed for engineering tissue in vitro and for human subject exercises. Results will benefit a large population of people who are vocally active but whose voices appear physiologically weak or aged.