Aspirin-loaded thermo-sensitive chitosan-sodium alginate hydrogel for the prevention of intrauterine adhesions

Intrauterine adhesions (IUAs) are fibrotic bands that form within the uterine cavity as a result of aberrant basal-endometrium repair following trauma or infection. Although several treatment modalities are available, recurrent adhesion remains frequent, and no preventive strategy has proven consistently reliable. In this work, we developed a β-Glycerophosphate-Chitosan/Sodium Alginate (β-GP-CS/SA) thermosensitive hydrogel incorporating aspirin (ASA) as a model anti-inflammatory compound. When exposed to physiological temperature (37 °C), the sol underwent gelation within approximately 5 min, forming an elastic gel (≈11.2 kPa) with an interconnected porous microarchitecture. The material underwent progressive biodegradation, losing nearly 87% of its mass in 14 days, while releasing about 60% of its ASA content in a sustained manner, indicating a release mechanism governed not solely by matrix erosion but also by diffusion and drug-polymer interactions. In vitro studies confirmed minimal cytotoxicity, suppression of fibrogenic markers (Collagen I and α-SMA), enhancement of VEGF expression, and promotion of stromal-cell migration. In vivo, implantation of the ASA-loaded gel markedly attenuated adhesion formation, preserved endometrial morphology, reduced stromal fibrosis, and produced no hepatic or renal lesions. These findings identify a biodegradable and thermoresponsive hydrogel that unites physical isolation with prolonged anti-inflammatory and regenerative actions, providing a rational basis for clinical prevention of IUAs.