posted on 2022-10-26, 12:03authored byR. Kevin Tindell, Michael J. McPhail, Cheryl E. Myers, Juergen Neubauer, Justin M. Hintze, David G. Lott, Julianne L. Holloway
The lamina propria within the vocal fold (VF) is a complex
multilayered
tissue that increases in stiffness from the superficial to deep layer,
where this characteristic is crucial for VF sound production. Tissue-engineered
scaffolds designed for VF repair must mimic the biophysical nature
of the native vocal fold and promote cell viability, cell spreading,
and vibration with air flow. In this study, we present a unique trilayered,
partially degradable hydrogel scaffold that mimics the multilayered
structure of the VF lamina propria. Using thiol-norbornene photochemistry,
trilayered hydrogel scaffolds were fabricated via layer-by-layer stacking
with increasing polymer concentration from the top to middle to deep
layer. Mechanical analysis confirmed that hydrogel modulus increased
with increasing polymer concentration. Partially degradable hydrogels
promoted high cell viability and cell spreading in three dimensions
as assessed via live/dead and cytoskeleton staining, respectively.
Importantly, partially degradable hydrogels maintained some degree
of the three dimensional polymer network following protease exposure,
while still enabling encapsulated cells to remodel their local environment
via protease secretion. Finally, the trilayered hydrogel scaffold
successfully vibrated and produced sound in proof-of-concept air flow
studies. This work represents a critical first step toward the design
of a multilayered, hydrogel scaffold for vocal fold tissue engineering.