Preparation and biological performance of a stepwise degradable hyaluronic acid hydrogel hemostatic sponge loaded with steroids

Chronic rhinosinusitis (CRS) is associated with postoperative complications such as adhesions and recurrent inflammation. Nasal implants are clinically utilized as adjuncts to endoscopic sinus surgery (ESS) for controlling hemorrhage and enhancing drug delivery. However, existing implants, such as NASOPORE®, exhibit uniform degradation patterns. In this study, we developed a stepwise degradable hyaluronic acid (HA) hydrogel hemostatic sponge loaded with mometasone furoate (Elocon Cream), designed to synchronize its degradation with the phases of wound healing. The sponge demonstrated a dual-phase degradation profile: rapid hemostatic material clearance (65 % mass loss by Day 5) followed by sustained HA hydrogel degradation (12 % residual mass at Day 14), enabling prolonged mucosal MF retention. The HA@F127-MF sponge exhibited exceptional water absorption (swelling ratio: 1470 ± 141 %), mechanical stability (compressive modulus: 12.8 ± 1.8 kPa), and controlled drug release (85.44 ± 3.22 % cumulative release over 15 days). In vivo studies revealed significant anti-inflammatory effects, with TNF-α, IL-5, and periostin levels reduced by 62 %, 68 %, and 54 %, respectively ( p < 0.01 vs. control), attributed to HA’s CD44-mediated anti-inflammatory activity (100 kDa) combined with MF’s corticosteroid action. Histological analysis confirmed minimal inflammation and no systemic toxicity. This study addresses critical limitations of current implants by introducing a stepwise degradable design that enhances hemostasis and sustained drug delivery, offering a promising strategy for CRS postoperative management.