Objectives: The extracellular matrix (ECM) of the vocal fold (VF) lamina propria—comprising collagen fibrils, elastin fibers, and glycosaminoglycans (GAGs)—regulates the phonatory behavior of the larynx. Collagen provides tensile strength, the elastin network confers flexibility, and hyaluronic acid (HA) contributes to tissue damping. Understanding the specific biomechanical roles of these ECM components is essential for the rational design of VF implants.
Methods: We developed a microengineered bioreactor platform to characterize the role of composite hydrogels capable of supporting cellular encapsulation for implantation during physiological functions. Our model includes collagen type I, gelatin methacryloyl (GelMA; serving as an elastin analog), and HA (serving as a GAGs analog) to recapitulate the native ECM. The concentration of each component was independently varied to assess its effect on phonatory parameters.
Results: We showed that a physiologically representative formulation (5% w/v collagen, 4% w/v GelMA, 0.8% w/v HA) has an elastic modulus of ~2 kPa, whereas pathological variations were generated by selectively increasing the hydrogel mass concentrations. For an elastic modulus of ~4 kPa, all pathological groups showed distinct shifts in the onset of fundamental frequency and phonation threshold.
Conclusions: Our results demonstrate that hierarchical ECM microarchitecture—not stiffness alone—governs phonatory biomechanics. These insights provide design principles for next-generation, biomimetic vocal fold implants. In addition, they can be used to design disease models such as VF fibrosis.