Thermosensitive hydrogel delivers nanoparticles for the modulation of immune homeostasis for salpingitis therapy

Salpingitis and subsequent conditions such as hydrosalpinx and tissue damage are significant causes of female infertility. Currently, beyond pharmacological and surgical interventions, there is a lack of highly effective therapeutic strategies, highlighting an urgent need for biomaterials that meet clinical demands. In this study, we developed a thermosensitive CS-RC-GP-ZnO hydrogel loaded with nanoparticles. This material undergoes a sol-gel transition at physiological temperature, enabling it to physically fill the infected fallopian tube while sustainably releasing antibacterial, anti-inflammatory, and pro-regenerative components. In vitro validation confirmed that CS-RC-GP-ZnO exhibits biocompatibility, biodegradability, the ability to promote cell proliferation and migration, induction of macrophage polarization, and effective antimicrobial properties. A rat model of salpingitis was established by combining mixed bacterial infection with mechanical injury. Using this model, CS-RC-GP-ZnO treatment was associated with activation of the cAMP/PKA/CREB pathway and a shift in macrophage-related markers toward an M2-like polarization state. This significantly enhances antibacterial and anti-inflammatory effects, promotes tissue repair, and subsequently remodels the immune microenvironment, thereby achieving notable therapeutic outcomes. In summary, the CS-RC-GP-ZnO hydrogel shows promising efficacy in treating salpingitis and other female reproductive diseases, indicating considerable potential for clinical translation. STATEMENT OF SIGNIFICANCE: To address the shortage of effective clinical therapies for salpingitis, a thermosensitive CS-RC-GP-ZnO hydrogel was developed by incorporating recombinant humanized collagen for enhanced tissue regeneration and zinc oxide nanoparticles for antibacterial and anti-inflammatory functions. A clinically relevant rat salpingitis model was established using mixed bacterial infection combined with mechanical injury to mimic ascending infection and pelvic inflammatory compression. The hydrogel restored immune homeostasis by synergistically promoting antibacterial activity, inflammation resolution, tissue repair, and macrophage polarization toward the M2 phenotype, offering a promising therapeutic strategy for salpingitis and related gynecological disorders.