Session: 01-03-01: General topics in vibrations and acoustics

Paper Number: 173083

A Miniaturized Hybrid Vocal Fold-on-a-Chip Platform for Pediatric Phonation Modeling 

Understanding pediatric phonation remains a critical challenge in voice biomechanics due to the anatomical and physiological differences between infant and adult vocal folds. Existing synthetic models have advanced our understanding of vocal fold aerodynamics and structure-function relationships but fall short in simulating biologically relevant microenvironments needed to study developmental phonation and disease. To address this limitation, we developed a miniaturized hybrid vocal fold-on-a-chip platform designed to integrate synthetic and biological materials, enabling both mechanical fidelity and bio-integrative capabilities.

Our platform is based on the downscaled EPI (epithelial-interfaced) model—a single-layered vocal fold design—reproduced at 1/4 scale to match infant vocal fold dimensions. The miniaturization not only replicates pediatric laryngeal anatomy but also reduces the required hydrogel volume and cellular input, a major advantage for future translational models using patient-derived cells. Using silicone elastomers blended with silicone thinner in ratios ranging from 1:1:0 to 1:1:1.5, we fabricated synthetic replicas exhibiting tunable stiffness within the physiological range of human vocal fold tissues. Rheological and mechanical tests demonstrated that increased thinner content led to lower Young’s modulus and storage modulus, favoring vibratory compliance.

Phonatory experiments showed that both geometry and material stiffness strongly influence subglottal pressure thresholds, sound pressure levels (SPL), glottal opening dynamics, and the fundamental frequency (F₀). Notably, 1/4EPI models with softer formulations (e.g., 1:1:1.5) exhibited successful self-sustained oscillation at lower subglottal pressures but with reduced acoustic output, underscoring the trade-off between phonation onset and vibratory efficiency. Across all scales, increasing airflow led to predictable rises in SPL and glottal area, with miniaturized replicas responding more dynamically. The 1/2EPI models showed the highest acoustic performance, while the 1/4EPI models more closely mirrored pediatric frequency ranges, reaching F₀ values above 1200 Hz.

To incorporate biologically relevant functionality, we introduced cell-laden GelMA (gelatin methacryloyl) hydrogels within the vocal fold replicas. Concentrations of 3–7% GelMA and Gelatin were tested under two base stiffness conditions (1% and 1.5% silicone thinner). Results revealed that GelMA constructs, especially at 5–7% concentrations, enhanced F₀ and SPL while maintaining mechanical integrity. Optical flow analysis, glottal kymography, and vocal fold trajectory tracking confirmed that hydrogel stiffness, volume, and placement critically influence vibratory behavior. Higher GelMA content and injection volumes resulted in more defined sinusoidal waveforms and increased oscillation amplitude.

Biological validation was achieved through cell viability assays using 3T3 fibroblasts encapsulated in GelMA. Constructs were exposed to airflow-induced oscillation for 2 hours daily over 7 days. Live/Dead staining and CCK-8 metabolic assays showed that short-term oscillation improved metabolic activity by Day 5. However, prolonged vibration led to localized cell death near the silicone–hydrogel interface, likely due to mechanical fatigue or leaching. Confocal imaging of Rhodamine diffusion further confirmed mechanoresponsive transport through the GelMA matrix under airflow, highlighting its utility as a tissue-mimetic scaffold.

This platform marks a significant advancement in vocal fold bioengineering, offering a tunable, scalable, and biologically integrable system for simulating pediatric phonation. The miniaturized design allows for high-throughput experimentation, while the hybrid construct supports mechanical-biological coupling, essential for studying mechanotransduction and tissue remodeling in developing vocal folds. The model is well-suited for future applications in disease modeling, drug screening, and tissue-engineered laryngeal grafts. Furthermore, its adaptability to various hydrogel systems and cell types paves the way for personalized, preclinical testing of regenerative therapies for pediatric voice disorders.

Presenting Author: Leila Donyaparastlivari New Jersey Institute of Technology

Presenting Author Biography: Graduate mechanical engineering student at New Jersey Institute of Technology

Authors:

Leila Donyaparastlivari New Jersey Institute of Technology
Rishi Kuriakose New Jersey Institute of Technology
Ayda Pourmostafa New Jersey Institute of Technology
Mohaddeseh Mohammadi New Jersey Institute of Technology
Daniel Li New Jersey Institute of Technology
Scott Thomson Brigham Young University-Idaho
Chen Shen Rowan University
Amir k.miri New Jersey Institute of Technology