ABSTRACT
Background: Liquid biomarkers have shown increasing utility in the clinical management of airway diseases. Salivary and blood samples are particularly amenable to point-of-care (POC) testing due to simple specimen collection and processing. However, very few POC tests have successfully progressed to clinical application due to the uncertainty and unpredictability surrounding their diagnostic accuracy. Objective: To review liquid biomarkers of airway diseases with well-established diagnostic accuracies and discuss their prospects for future POC applications. Methodology: A literature review of publications indexed in Medline or Embase was performed to evaluate the diagnostic accuracy of liquid biomarkers for chronic obstructive pulmonary disease (COPD), asthma, laryngopharyngeal reflux (LPR), and COVID-19. Results: Of 3,628 studies, 71 fulfilled the inclusion criteria. Sputum and blood eosinophils were the most frequently investigated biomarkers for the management of asthma and COPD. Salivary pepsin was the only biomarker with a well-documented accuracy for the diagnosis of LPR. Inflammatory blood biomarkers (e.g., CRP, D-dimers, ferritin) were found to be useful to predict the severity, complications, and mortality related to COVID-19 infection. Conclusion: Multiple liquid biomarkers have well-established diagnostic accuracies and are thus amenable to POC testing in clinical settings.
ABSTRACT
Vocal folds, housed in the upper respiratory tract, are important to daily breathing, speech and swallowing functions. Irreversible changes to the vocal fold mucosae, such as scarring and atrophy, require a regenerative medicine approach to promote a controlled regrowth of the extracellular matrix (ECM)-rich mucosa. Various biomaterial systems have been engineered with an emphasis on stimulating local vocal fold fibroblasts to produce new ECM. At the same time, it is imperative to limit the foreign body reaction and associated immune components that can hinder the integration of the biomaterial into the host tissue. Modern biomaterial designs have become increasingly focused on actively harnessing the immune system to accelerate and optimize the process of tissue regeneration. An array of physical and chemical biomaterial parameters have been reported to effectively modulate local immune cells, such as macrophages, to initiate tissue repair, stimulate ECM production, promote biomaterial-tissue integration, and restore the function of the vocal folds. In this perspective paper, the unique immunological profile of the vocal folds will first be reviewed. Key physical and chemical biomaterial properties relevant to immunomodulation will then be highlighted and discussed. A further examination of the physicochemical properties of recent vocal fold biomaterials will follow to generate deeper insights into corresponding immune-related outcomes. Lastly, a perspective will be offered on the opportunity of integrating material-led immunomodulatory strategies into future vocal fold tissue engineering therapies.
ABSTRACT
The physical properties of a biomaterial play an essential role in regulating immune and reparative activities within the host tissue. This study aimed to evaluate the immunological impact of material stiffness of a glycol-chitosan hydrogel designed for vocal fold tissue engineering. Hydrogel stiffness was varied via the concentration of glyoxal cross-linker applied. Hydrogel mechanical properties were characterized through atomic force microscopy and shear plate rheometry. Using a transwell setup, macrophages were co-cultured with human vocal fold fibroblasts that were embedded within the hydrogel. Macrophage viability and cytokine secretion were evaluated at 3, 24, and 72 hr of culture. Flow cytometry was applied to evaluate macrophage cell surface markers after 72 hr of cell culture. Results indicated that increasing hydrogel stiffness was associated with increased anti-inflammatory activity compared to relevant controls. In addition, increased anti-inflammatory activity was observed in hydrogel co-cultures. This study highlighted the importance of hydrogel stiffness from an immunological viewpoint when designing novel vocal fold hydrogels.
