Research progress and applications of functional hydrogels in nasal wound healing.

Nasal wound healing presents a distinct clinical challenge in otorhinolaryngology, complicated by the unique physicochemical environment of the nasal cavity-including a slightly acidic mucosal pH (≈ 6.3-6.9), shear-thinning mucus rheology (healthy viscosity ≈ 0.1-1 Pa·s, elevated to 1.6-3.2 Pa·s in chronic sinusitis), continuous mucociliary clearance (MCC) with ciliary beat frequencies of ~ 10 Hz, and enzymatic activity dominated by lysozyme. Conventional nasal packing materials-such as Vaseline gauze and polyvinyl alcohol sponges-suffer from poor biocompatibility, rigid mechanical properties, and traumatic removal, failing to satisfy these demanding physicochemical constraints. Functional hydrogels, owing to their tunable viscoelasticity, dynamic covalent or supramolecular crosslinking, and intrinsic responsiveness to pH, reactive oxygen species (ROS), temperature, and enzymes, have emerged as a next-generation solution. This review systematically profiles the physicochemical microenvironment of the nasal wound; reclassifies hydrogel systems by polymer backbone (natural polysaccharides/proteins vs. synthetic polymers) and crosslinking chemistry (dynamic covalent bonds: Schiff base, disulfide, boronic ester vs. supramolecular: host-guest, hydrogen bonding); and examines reaction pathways, degradation kinetics, and mechanical matching with nasal mucosa. Representative systems are critically evaluated, including: (i) the RADA16 self-assembling peptide hydrogel, which in randomized clinical trials reduced postoperative adhesion by 91-100% compared with gelatin-thrombin and bioresorbable controls; (ii) TSPBA/PVA ROS-responsive hydrogels that scavenge H₂O₂ via boronic ester cleavage (second-order rate constant ≈ 0.1-1 M⁻¹·s⁻¹), prolonging mucosal retention to 24 h; (iii) pNIPAAm-based thermoresponsive systems with LCST ≈ 32 °C, the critical implications of which for the physiological nasal temperature range (30-34 °C) are discussed. We further analyze cell-material interactions governing macrophage M1→M2 polarization, epithelial/fibroblast behavior, and ciliary function. Ongoing clinical trials (NCT04970966, NCT05898074) and persistent translational challenges-including sterilization, long-term in vivo safety, and standardized large-scale production-are critically addressed, offering a materials-science-focused framework for the design of next-generation nasal hydrogels.