A Patient-Specific in silico Model of Inflammation and Healing Tested in Acute Vocal Fold Injury

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

The Response of Vocal Fold Fibroblasts and Mesenchymal Stromal Cells to Vibration

Illumination of cellular changes caused by mechanical forces present within the laryngeal microenvironment may well guide strategies for tissue engineering the vocal fold lamina propria. The purpose of this study was to compare the response of human vocal fold fibroblasts (hVFF) and bone marrow mesenchymal stem cells (BM-MSC) to vibratory stimulus. In order to study these effects, a bioreactor capable of vibrating two cell seeded substrates was developed. The cell seeded substrates contact each other as a result of the sinusoidal frequency, producing a motion similar to the movement of true vocal folds. Utilizing this bioreactor, hVFF and BM-MSC were subjected to 200 Hz vibration and 20% strain for 8 hours. Immunohistochemistry (Ki-67 and TUNEL) was performed to examine cell proliferation and apoptosis respectively, while semi-quantitative RT-PCR was used to assess extracellular matrix related gene expression. HVFF significantly proliferated (p = 0.011) when subjected to 200 Hz vibration and 20% strain, while BM-MSC did not (p = 1.0). A statistically significant increase in apoptosis of BM-MSC (p = 0.0402) was observed under the experimental conditions; however high cell viability (96%) was maintained. HVFF did not have significantly altered apoptosis (p = 0.7849) when subjected to vibration and strain. Semi-quantitative RT-PCR results show no significant differences in expression levels of collagen I (BM-MSC p = 0.1951, hVFF p = v0.3629), fibronectin (BM-MSC p = 0.1951, hVFF p = 0.2513), and TGF-β1 (BM-MSC p = 0.2534, hVFF p = 0.6029) between vibratory and static conditions in either cell type. Finally, smooth muscle actin mRNA was not present in either vibrated or static samples, indicating that no myofibroblast differentiation occurred for either cell type. Together, these results demonstrate that BM-MSC may be a suitable alternative to hVFF for vocal fold tissue engineering. Further investigation into a larger number of gene markers, protein levels, increased number of donors and vibratory conditions are warranted

A novel antimicrobial lectin from Eugenia malaccensis that stimulates cutaneous healing in mice model

Objective The present work reports the purification and partial characterization of an antibacterial lectin (EmaL) obtained from Eugenia malaccensis seeds as well as the evaluation of its effect in the daily topical treatment of repairing process of cutaneous wounds in mice. Materials and methods The cutaneous wound was produced by the incision of the skin and use of lectin in the treatment of mice cutaneous wounds was evaluated. Surgical wounds were treated daily with a topical administration of EmaL and parameters such as edema, hyperemia, scab, granulation and scar tissues as well as contraction of wounds were analyzed. Results A novel lectin, with a molecular mass of 14 kDa, was isolated from E. malaccensis using affinity chromatography. The lectin (EmaL) agglutinated glutaraldehyde-treated rabbit and human erythrocytes; the lectin-induced rabbit erythrocyte agglutination was inhibited by glucose, casein, ovalbumin and fetuin. Also, Emal was very effective in the inhibition of bacterial growth, with the best inhibition results obtained for Staphylococcus aureus. Inflammatory signals such as edema and hyperemia were statistically less intense when EmaL was applied compared to the control. The histopathological analysis showed that the treated injured tissue presented reepithelialization (complete or partial) and areas of transition more evidenced than those of the control group, especially due to well organized pattern of collagen fibers presented in the granulation fibrous tissue. Conclusion Presented results are a preliminary indication of the pharmacological interest in using EmaL as antimicrobial agent and in the repairing process of cutaneous wounds.This paper was financially supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), FACEPE and CAPES, Brazil. The authors are deeply grateful for the technical assistance of Maria Barbosa Reis da Silva and João Antonio Virgínio and Alfa/VALNATURA Project.info:eu-repo/semantics/publishedVersio