Airway Resistance and Respiratory Distress in Laryngeal Cancer: A Computational Fluid Dynamics Study.

BACKGROUND: Obstructive upper airway pathologies are a great clinical challenge for the airway surgeon. Protection against acute obstruction is critical, but avoidance of unnecessary tracheostomy must also be considered. Decision-making regarding airway, although supported by some objective findings, is largely guided by subjective experience and training. This investigation aims to study the relationship between clinical respiratory distress and objective measures of airway resistance in laryngeal cancer as determined by computational fluid dynamic (CFD) and morphometric analysis. METHODS: Retrospective CT and clinical data were obtained for series of 20 cases, defined as newly diagnosed laryngeal cancer patients who required admission or urgent airway surgery, and 20 controls. Cases and controls were matched based on T-staging. Image segmentation and morphometric analysis were first performed. Computational models based on the lattice Boltzmann method were then created and used to quantify the continuous mass flow, rigid wall, and constant static pressure inlet boundary conditions. RESULTS: The analysis demonstrated a significant relationship between airway resistance and acute obstruction (OR 1.018, 95% CI 1.001-1.045). Morphometric analysis similarly demonstrated a significant relationship when relating measurements based on the minimum cross-section, but not on length of stenosis. Morphometric measurements also showed significance in predicting CFD results, and their relationship demonstrated that airway pressures increase exponentially below 2.5 mm. Tumor subsite did not show a significant difference, although the glottic subgroup tended to have higher resistances. CONCLUSION: Airway resistance analysis from CFD computation correlated with presence of acute distress requiring emergent management. Morphometric analysis showed a similar correlation, demonstrating a radiologic airway assessment technique on which future risk estimation could be performed. LEVEL OF EVIDENCE: 4 (case-control study) Laryngoscope, 133:2734-2741, 2023.

Efficacy of Aerosol Reduction Measures for Dental Aerosol Generating Procedures.

Aerosol particles generated by dental procedures could facilitate the transmission of infectious diseases and contain carcinogen particles. Such particles can penetrate common surgical masks and reach the lungs, leading to increased risk for dental care professionals. However, the risk of inhaling contaminated aerosol and the effectiveness of aerosol reduction measures in dental offices remain unclear. The present study aimed to quantify aerosols produced by drilling and scaling procedures and to evaluate present recommendations for aerosol reduction. The concentration of aerosol particles released from the mock scaling and drilling procedures on dental mannequin were measured using a TSI Optical Particle Sizer (OPS 3330) during 15-min sessions carried out in a single-patient examination room. Using a drilling procedure as the aerosol source, the aerosol reduction performance of two types of high-volume evacuators (HVEs) and a commercial off-the-shelf air purifier was evaluated in a simulated clinical setting. Using either HVEs or the air purifier individually reduced the aerosol accumulated over the course of a 15-minutes drilling procedure at a reduction rate of 94.8 to 97.6%. Using both measures simultaneously raised the reduction rate to 99.6%. The results show that existing HVEs can effectively reduce aerosol concentration generated by a drilling procedure and can be further improved by using an air purifier. Following current regulatory guidelines can ensure a low risk of inhaling contaminated aerosol for dentists, assistants, and patients.

Decellularized Extracellular Matrix Composite Hydrogel Bioinks for the Development of 3D Bioprinted Head and Neck in Vitro Tumor Models.

Reinforced extracellular matrix (ECM)-based hydrogels recapitulate several mechanical and biochemical features found in the tumor microenvironment (TME) in vivo. While these gels retain several critical structural and bioactive molecules that promote cell-matrix interactivity, their mechanical properties tend toward the viscous regime limiting their ability to retain ordered structural characteristics when considered as architectured scaffolds. To overcome this limitation characteristic of pure ECM hydrogels, we present a composite material containing alginate, a seaweed-derived polysaccharide, and gelatin, denatured collagen, as rheological modifiers which impart mechanical integrity to the biologically active decellularized ECM (dECM). After an optimization process, the reinforced gel proposed is mechanically stable and bioprintable and has a stiffness within the expected physiological values. Our hydrogel's elastic modulus has no significant difference when compared to tumors induced in preclinical xenograft head and neck squamous cell carcinoma (HNSCC) mouse models. The bioprinted cell-laden model is highly reproducible and allows proliferation and reorganization of HNSCC cells while maintaining cell viability above 90% for periods of nearly 3 weeks. Cells encapsulated in our bioink produce spheroids of at least 3000 µm2 of cross-sectional area by day 15 of culture and are positive for cytokeratin in immunofluorescence quantification, a common marker of HNSCC model validation in 2D and 3D models. We use this in vitro model system to evaluate the standard-of-care small molecule therapeutics used to treat HNSCC clinically and report a 4-fold increase in the IC50 of cisplatin and an 80-fold increase for 5-fluorouracil compared to monolayer cultures. Our work suggests that fabricating in vitro models using reinforced dECM provides a physiologically relevant system to evaluate malignant neoplastic phenomena in vitro due to the physical and biological features replicated from the source tissue microenvironment.

Triggered micropore-forming bioprinting of porous viscoelastic hydrogels.

Cell-laden scaffolds of architecture and mechanics that mimic those of the host tissues are important for a wide range of biomedical applications but remain challenging to bioprint. To address these challenges, we report a new method called triggered micropore-forming bioprinting. The approach can yield cell-laden scaffolds of defined architecture and interconnected pores over a range of sizes, encompassing that of many cell types. The viscoelasticity of the bioprinted scaffold can match that of biological tissues and be tuned independently of porosity and stiffness. The bioprinted scaffold also exhibits superior mechanical robustness despite high porosity. The bioprinting method and the resulting scaffolds support cell spreading, migration, and proliferation. The potential of the 3D bioprinting system is demonstrated for vocal fold tissue engineering and as an in vitro cancer model. Other possible applications are foreseen for tissue repair, regenerative medicine, organ-on-chip, drug screening, organ transplantation, and disease modeling.

Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification.

Agent based models (ABM) were developed to numerically simulate the biological response to surgical vocal fold injury and repair at the physiological level. This study aimed to improve the representation of existing ABM through a combination of empirical and computational experiments. Empirical data of vocal fold cell populations including neutrophils, macrophages and fibroblasts were obtained using flow cytometry up to four weeks following surgical injury. Random Forests were used as a sensitivity analysis method to identify model parameters that were most influential to ABM outputs. Statistical Parameter Optimization Tool for Python was used to calibrate those parameter values to match the ABM-simulation data with the corresponding empirical data from Day 1 to Day 5 following surgery. Model performance was evaluated by verifying if the empirical data fell within the 95% confidence intervals of ABM outputs of cell quantities at Day 7, Week 2 and Week 4. For Day 7, all empirical data were within the ABM output ranges. The trends of ABM-simulated cell populations were also qualitatively comparable to those of the empirical data beyond Day 7. Exact values, however, fell outside of the 95% statistical confidence intervals. Parameters related to fibroblast proliferation were indicative to the ABM-simulation of fibroblast dynamics in final stages of wound healing.

Multimodal virtual histology of rabbit vocal folds by nonlinear microscopy and nano computed tomography.

Human vocal folds (VFs) possess a unique anatomical structure and mechanical properties for human communication. However, VFs are prone to scarring as a consequence of overuse, injury, disease or surgery. Accumulation of scar tissue on VFs inhibits proper phonation and leads to partial or complete loss of voice, with significant consequences for the patient's quality of life. VF regeneration after scarring provides a significant challenge for tissue engineering therapies given the complexity of tissue microarchitecture. To establish an effective animal model for VF injury and scarring, new histological methods are required to visualize the wound repair process of the tissue in its three-dimensional native environment. In this work, we propose the use of a combination of nonlinear microscopy and nanotomography as contrast methods for virtual histology of rabbit VFs. We apply these methods to rabbit VF tissue to demonstrate their use as alternatives to conventional VF histology that may enable future clinical studies of this injury model.

Development and validation of a 3D-printed model of the ostiomeatal complex and frontal sinus for endoscopic sinus surgery training.

BACKGROUND: Endoscopic sinus surgery poses unique training challenges due to complex and variable anatomy, and the risk of major complications. We sought to create and provide validity evidence for a novel 3D-printed simulator of the nose and paranasal sinuses. METHODS: Sinonasal computed tomography (CT) images of a patient were imported into 3D visualization software. Segmentation of bony and soft tissue structures was then performed. The model was printed using simulated bone and soft tissue materials. Rhinologists and otolaryngology residents completed 6 prespecified tasks including maxillary antrostomy and frontal recess dissection on the simulator. Participants evaluated the model using survey ratings based on a 5-point Likert scale. The average time to complete each task was calculated. Descriptive analysis was used to evaluate ratings, and thematic analysis was done for qualitative questions. RESULTS: A total of 20 participants (10 rhinologists and 10 otolaryngology residents) tested the model and answered the survey. Overall the participants felt that the simulator would be useful as a training/educational tool (4.6/5), and that it should be integrated as part of the rhinology training curriculum (4.5/5). The following responses were obtained: visual appearance 4.25/5; realism of materials 3.8/5; and surgical experience 3.9/5. The average time to complete each task was lower for the rhinologist group than for the residents. CONCLUSION: We describe the development and validation of a novel 3D-printed model for the training of endoscopic sinus surgery skills. Although participants found the simulator to be a useful training and educational tool, further model development could improve the outcome.

Fracture Toughness of Vocal Fold Tissue: A Preliminary Study.

A customized mechanical tester that slices thin, soft samples was used to measure the fracture toughness of vocal fold tissue. Porcine vocal fold lamina propria was subjected to quasi-static, guillotine-like tests at three equally distanced regions along the anterior-posterior direction. The central one-third where high-velocity collisions between vocal folds occur was found to have the maximum fracture toughness. In contrast, the anterior one-third featured a lower toughness. Fracture toughness can be indicative of the risk of benign and malignant lesions in vocal fold tissue.

An in vivo study of composite microgels based on hyaluronic acid and gelatin for the reconstruction of surgically injured rat vocal folds.

PURPOSE The objective of this study was to investigate local injection with a hierarchically microstructured hyaluronic acid-gelatin (HA-Ge) hydrogel for the treatment of acute vocal fold injury using a rat model. METHOD Vocal fold stripping was performed unilaterally in 108 Sprague-Dawley rats. A volume of 25 µl saline (placebo controls), HA-bulk, or HA-Ge hydrogel was injected into the lamina propria (LP) 5 days after surgery. The vocal folds were harvested at 3, 14, and 28 days after injection and analyzed using hematoxylin and eosin staining and immunohistochemistry staining for macrophages, myofibroblasts, elastin, collagen type I, and collagen type III. RESULTS The macrophage count was statistically significantly lower in the HA-Ge group than in the saline group (p < .05) at Day 28. Results suggested that the HA-Ge injection did not induce inflammatory or rejection response. Myofibroblast counts and elastin were statistically insignificant across treatment groups at all time points. Increased elastin deposition was qualitatively observed in both HA groups from Day 3 to Day 28, and not in the saline group. Significantly more elastin was observed in the HA-bulk group than in the uninjured group at Day 28. Significantly more collagen type I was observed in the HA-bulk and HA-Ge groups than in the saline group (p < .05) at Day 28. The collagen type I concentration in the HA-Ge and saline groups was found to be comparable to that in the uninjured controls at Day 28. The concentration of collagen type III in all treatment groups was similar to that in uninjured controls at Day 28. CONCLUSION Local HA-Ge and HA-bulk injections for acute injured vocal folds were biocompatible and did not induce adverse response.

Unsteady numerical simulation of a round jet with impinging microjets for noise suppression.

The objective of this study was to determine the feasibility of a lattice-Boltzmann method (LBM)-Large Eddy Simulation methodology for the prediction of sound radiation from a round jet-microjet combination. The distinct advantage of LBM over traditional computational fluid dynamics methods is its ease of handling problems with complex geometries. Numerical simulations of an isothermal Mach 0.5, Re(D) = 1 × 10(5) circular jet (D(j) = 0.0508 m) with and without the presence of 18 microjets (D(mj) = 1 mm) were performed. The presence of microjets resulted in a decrease in the axial turbulence intensity and turbulent kinetic energy. The associated decrease in radiated sound pressure level was around 1 dB. The far-field sound was computed using the porous Ffowcs Williams-Hawkings surface integral acoustic method. The trend obtained is in qualitative agreement with experimental observations. The results of this study support the accuracy of LBM based numerical simulations for predictions of the effects of noise suppression devices on the radiated sound power.

Vocal fold vibration measurements using laser Doppler vibrometry.

The objective of this study was to measure the velocity of the superior surface of human vocal folds during phonation using laser Doppler vibrometry (LDV). A custom-made endoscopic laser beam deflection unit was designed and fabricated. An in vivo clinical experimental procedure was developed to simultaneously collect LDV velocity and video from videolaryngoscopy. The velocity along the direction of the laser beam, i.e., the inferior-superior direction, was captured. The velocity was synchronous with electroglottograph and sound level meter data. The vibration energy of the vocal folds was determined to be significant up to a frequency of 3 kHz. Three characteristic vibrational waveforms were identified which may indicate bifurcations between vibrational modes of the mucosal wave. No relationship was found between the velocity amplitude and phonation frequency or sound pressure level. A correlation was found between the peak-to-peak displacement amplitude and phonation frequency. A sparse map of the velocity amplitudes on the vocal fold surface was obtained.