In vitro evaluation of a novel oxygen‐generating biomaterial for chronic rhinosinusitis therapy

Abstract

Background Hypoxia due to closure at the ostiomeatal complex is widely considered one of the major pathogenic mechanisms leading to chronic inflammation in chronic rhinosinusitis (CRS). The objective of this study was to develop and characterize an oxygen‐generating biomaterial (OGB) as an innovative treatment strategy for CRS. Methods An OGB was fabricated by coating hydrophobic beeswax (BW, 15mg or 30mg) on the surface of calcium peroxide ‐ catalase complex (CPO‐CA, 30mg) and characterized using scanning electron microscopy (SEM). In vitro releases of both oxygen and hydrogen peroxide (H2O2) were spectrophotometrically quantified, and cytotoxicity in human sinonasal epithelial cells (HSNECs) was evaluated. The influence of OGB on transepithelial Cl– secretion was also determined by pharmacologically manipulating HSNECs, cultured under hypoxic conditions, in Ussing chambers. Results Three groups of OGBs: (1) CPO only; (2) CPO coated with CA and BW (1:1 ratio, CPO‐CA(1)‐BW(1)); and (3) CPO coated with CA and BW (1:0.5 ratio, CPO‐CA(1)‐BW(0.5) were analyzed for accumulated oxygen release over 7 days: highest release (mmol/mg) was observed in CPO‐CA(1)‐BW(1) = 0.11 ± 0.003, followed by CPO‐CA(1)‐BW(0.5) = 0.08 ± 0.010, and CPO = 0.05 ± 0.004 (p < 0.0001). H2O2 production (mM) was significantly higher in CPO (1.87 ± 0.50) compared to CPO‐CA (1)‐BW(1) (0.00 ± 0.00) (p < 0.001) after 24 h. CPO‐CA(1)‐BW(1) showed significantly reduced cytotoxicity and increased Cl– transport compared to the CPO group. Conclusion A novel OGB (CPO‐CA‐BW complex) exhibited sustained oxygen release over 7 days without significant cytotoxicity after 24 h in vitro. Preclinical studies evaluating the efficacy of OGB in CRS are warranted, especially for potential therapy in an obstruction‐based CRS model.

Hypoxia‐induced cystic fibrosis transmembrane conductance regulator dysfunction is a universal mechanism underlying reduced mucociliary transport in sinusitis

“…37,46,47,[50][51][52][53][54][55] Additionally, methods to oxygenate the sinuses and the underlying mucosa using surgical strategies and/or oxygen-generating biomaterials are reasonable approaches to mitigate the impact of hypoxia. 56 As we have noted previously, ROS scavengers like glutathione could play a role in mitigating the early impact of obstruction-induced hypoxia. 15 Indeed, topical inhaled ROS scavengers are already clinically approved, such as the redox agent N-acetyl cysteine, which has been used to remove mucus plugs in CF and other respiratory diseases of mucus obstruction.…”

Changes in serum hypoxia-inducible factor-1α and erythropoietin in allergic rhinitis patients: Correlation with the Th inflammatory profile and disease comorbidities

“… 32 Hypoxia due to closure at the ostiomeatal complex is widely considered one of the major pathogenic mechanisms leading to chronic inflammation in chronic rhinosinusitis. 33 A positive relationship is detected between each of HIF-1α and HIF-2α protein expression in epithelial cells and the endoscopic score in nasal polyp samples. However, there is a negative correlation between HIF-1α expression and each of the degree of eosinophil infiltration and IL-17A expression.…”

Glutathione and bicarbonate nanoparticles improve mucociliary transport in cystic fibrosis epithelia

“…Medium was collected at each time point and LDH was measured as an indicator of cellular toxicity using CyQUANT LDH Cytotoxicity Assay Kit (Cat#C20301; Invitrogen) as previously described. [30][31][32]…”