Understanding voice problems: A physiological perspective for diagnosis and treatment

Wound Healing: Biochemical and Clinical Aspects

The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains.

/pdf/a-patient-specific-in-silico-model-of-inflammation-and-3glflkb1tw.pdf

A patient-specific in silico model of inflammation and healing tested in acute vocal fold injury.

Background— The cytokine interleukin (IL)-1 is an important mediator of inflammation and cardiovascular disease. Activity of this cytokine is modulated endogenously via the IL-1 receptor antagonist (IL-1Ra). The role of IL-1Ra in neointima formation after injury, however, is poorly understood. Methods and Results— Using IL-1Ra–deficient (IL-1Ra−/−; backcrossed 8 generations into the C57BL/6J background) and wild-type (IL-1Ra+/+) mice, we investigated neointimal formation 3 weeks after femoral artery injury induced by an external vascular cuff model. Intima and media thicknesses were measured, and the intima/media ratio was calculated. The mean intimal thickness and the intima/media ratio of IL-1Ra−/− mice increased by 249% (31.8±2.9 μm [n=10] versus 9.1±0.7 μm [n=10]; P<0.0001) and 257% (2.5±0.2 versus 0.7±0.1; P<0.0001), respectively, compared with IL-1Ra+/+ mice. No significant differences were observed in the medial thickness. Control immunostaining for IL-1Ra in injured vessels localized IL-1β and the...

Deficiency of Interleukin-1 Receptor Antagonist Promotes Neointimal Formation After Injury

/pdf/biosimulation-of-vocal-fold-inflammation-and-wound-healing-41ivil8rfj.pdf

Biosimulation of vocal fold inflammation and wound healing

The role of exercise in vocal fold wound healing has been overlooked. Data from numerous other systems suggest a positive role of tissue mobilization to facilitate optimal wound healing and biomechanically superior tissue. The current study sought to investigate the potential role of mechanical signaling to attenuate the inflammatory and alter the synthetic properties of fibroblasts cultured from the vocal folds. Vocal fold fibroblasts were subjected to one of four conditions: no treatment, IL-1â alone, mechanical stress alone, or mechanical stress plus IL-1â. Results suggest that mechanical stress may limit the inflammatory phenotype of vocal fold fibroblasts in the short-term (4 hours), but not in the long-term (24 hours). In fact, 24 hours of mechanical stress may actually increase the inflammatory response. In addition, neither IL-1â nor mechanical stress had an effect on vocal fold fibroblast synthesis of extracellular matrix proteins. As a potential explanation for the current findings, it is hypothesized that the vocal folds may be more resilient to mechanical stress given the inherently stressful environment associated with phonation.

/pdf/vocal-fold-fibroblast-response-to-mechanical-stress-55a3h5p1w8.pdf

Vocal Fold Fibroblast Response to Mechanical Stress

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Vocal Fold Fibroblast Response to Mechanical Stress