Neubauer, Juergen

The lamina propria within the vocal fold (VF) is a complex multi-layered 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 tri-layered, partially-degradable hydrogel scaffold that mimics the multi-layered structure of the VF lamina propria. Using thiol-norbornene photochemistry, tri-layered hydrogel scaffolds were fabricated via layer-by-layer stacking with increasing polymer concentration from the top to middle to deep layer. Mechanical analysis confirmed hydrogel modulus increased with increasing polymer concentration. Partially-degradable hydrogels promoted high cell viability and cell spreading in 3D as assessed via live/dead and cytoskeleton staining, respectively. Importantly, partially-degradable hydrogels maintained some degree of the 3D polymer network following protease exposure, while still enabling encapsulated cells to remodel their local environment via protease secretion. Finally, the tri-layered hydrogel scaffold successfully vibrated and produced sound in proof-of-concept air flow studies. This work represents a critical first step towards the design of a multi-layered, hydrogel scaffold for vocal fold tissue engineering.

Objectives/HypothesisDevelop a patient‐specific tissue engineered construct for laryngeal reconstruction following a partial laryngectomy.Study DesignBench and animal research.MethodsA construct made from a porous polyethylene scaffold shaped in a canine‐specific configuration and seeded with autologous canine adipose‐derived stem cells in fibrin glue was implanted in a canine following a partial laryngectomy. After 1 year, the construct was first evaluated in vivo with high‐speed imaging and acoustic–aerodynamic measures. It was then explanted and evaluated histologically.ResultsThe canine study at 1 year revealed the construct provided voicing (barking) with acoustic and aerodynamic measures within normal ranges. The canine was able to eat and breathe normally without long‐term support. The construct was integrated with epithelialization of all areas except the medial portion of the vocal fold structure. No anti‐infective agents were needed after the standard perioperative medications were completed.ConclusionThis study provided a successful first step toward developing a patient‐specific composite construct for patients undergoing partial laryngectomies.Level of EvidenceNA Laryngoscope, 132:S1–S11, 2022