Supramolecular gel with enhanced immunomodulatory effects presents a minimally invasive treatment strategy for eosinophilic chronic rhinosinusitis

Background: Chronic rhinosinusitis (CRS) is an inflammatory disease characterized by persistent immune dysregulation, which presents considerable limitations in current medical therapy.

Objects: This study investigates a supramolecular gel (PSPD), which aims to minimize systemic adverse effects through local injection, provide long-lasting anti-inflammatory effects, and modulate the mucosal immune microenvironment.

Methods: The properties of PSPD were evaluated using rheological experiments. Biocompatibility assessments were conducted through CCK-8 and serum biochemical analyses. The balance between T_H17 and Treg was determined using immunofluorescence (IF) and flow cytometry (FC). Additionally, sinus computed tomography (CT), and endoscopy were employed to evaluate mucosal swelling.

Results: Rheological assessments revealed that PSPD possesses excellent self-healing and slow-release properties. CCK-8 and serum biochemical assays indicated that PSPD demonstrated superior biocompatibility. In nasal polyps, PSPD significantly inhibited IL17 expression. In an Eosinophilic Chronic Rhinosinusitis (ECRS) rat model, treatment with PSPD led to significant alleviation of nasal mucosal congestion. Furthermore, PSPD modulated the proliferation of T_H17 and Treg as well as the expression of cytokines, ultimately reversing the T_H17/Treg immune imbalance.

Conclusion: This multifunctional gel effectively sustains the modulation of T_H17/Treg homeostasis, improving long-term disease management and representing a promising new therapeutic strategy for CRS, particularly in cases of ECRS.