Biosimulation of inflammation and healing in surgically injured vocal folds.
OBJECTIVE
The pathogenesis of vocal fold scarring is complex and remains to be deciphered. The current study is part of research endeavors aimed at applying systems biology approaches to address the complex biological processes involved in the pathogenesis of vocal fold scarring and other lesions affecting the larynx.


METHODS
We developed a computational agent-based model (ABM) to quantitatively characterize multiple cellular and molecular interactions involved in inflammation and healing in vocal fold mucosa after surgical trauma. The ABM was calibrated with empirical data on inflammatory mediators (eg, tumor necrosis factor) and extracellular matrix components (eg, hyaluronan) from published studies on surgical vocal fold injury in the rat population.


RESULTS
The simulation results reproduced and predicted trajectories seen in the empirical data from the animals. Moreover, the ABM studies suggested that hyaluronan fragments might be the clinical surrogate of tissue damage, a key variable that in these simulations both is enhanced by and further induces inflammation.


CONCLUSIONS
A relatively simple ABM such as the one reported in this study can provide new understanding of laryngeal wound healing and generate working hypotheses for further wet-lab studies.
Li
Nicole Y K
NY
Department of Communication Science and Disorders, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Vodovotz
Yoram
Y
Hebda
Patricia A
PA
Abbott
Katherine Verdolini
KV
D000818:Animals; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D049490:Systems Biology; D014827:Vocal Cords / Q000276:immunology* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000502:physiology*