Functional Hydrogels, including RADA16, Offer Advanced Solutions for Complex Nasal Wound Healing

Healing nasal wounds presents unique challenges in otorhinolaryngology due to the nasal cavity's specific physicochemical environment, including a slightly acidic mucosal pH (≈ 6.3-6.9), shear-thinning mucus rheology (healthy viscosity ≈ 0.1-1 Pa·s), continuous mucociliary clearance (MCC) at ~ 10 Hz, and high enzymatic activity from lysozyme. Conventional packing materials like Vaseline gauze and polyvinyl alcohol sponges are inadequate, suffering from poor biocompatibility, rigid mechanical properties, and traumatic removal, failing to meet these demanding constraints. Functional hydrogels, with their tunable viscoelasticity, dynamic crosslinking, and responsiveness to stimuli like pH, reactive oxygen species (ROS), and temperature, emerge as a promising next-generation solution.

This review systematically profiled the physicochemical microenvironment of nasal wounds, reclassifying hydrogel systems based on their polymer backbone (natural polysaccharides/proteins vs. synthetic polymers) and crosslinking chemistry (dynamic covalent bonds like Schiff base, disulfide, boronic ester vs. supramolecular interactions like host-guest, hydrogen bonding). The authors examined critical aspects such as reaction pathways, degradation kinetics, and mechanical matching with nasal mucosa. Representative systems were critically evaluated, including the RADA16 self-assembling peptide hydrogel, TSPBA/PVA ROS-responsive hydrogels, and pNIPAAm-based thermoresponsive systems.

The review identified functional hydrogels as a superior alternative to traditional nasal packing. Key findings highlighted the efficacy of specific hydrogel systems:

The RADA16 self-assembling peptide hydrogel, in randomized clinical trials, significantly reduced postoperative adhesion by 91-100% when compared with gelatin-thrombin and bioresorbable controls. TSPBA/PVA ROS-responsive hydrogels demonstrated the ability to scavenge H₂O₂ via boronic ester cleavage, with a second-order rate constant of ≈ 0.1-1 M⁻¹·s⁻¹, which prolonged mucosal retention to 24 hours. Furthermore, pNIPAAm-based thermoresponsive systems, characterized by a LCST (Lower Critical Solution Temperature) of ≈ 32 °C, were discussed for their critical implications within the physiological nasal temperature range of 30-34 °C, suggesting their potential for on-demand gelation and drug release.