Background: Preterm birth is a common cause of morbidity and mortality in newborn infants. Cervical insufficiency (CI) is a significant cause of preterm birth. The treatment for CI is cerclage, which is a suture placed around the cervix to provide mechanical support. Cerclage, however, is associated with limited efficacy. Here we present an injectable, silk-based hydrogel as an alternative to cerclage. Objective: Pregnant rabbits were used as an animal model of pregnancy to study the mechanical properties, biocompatibility, and degradation of the hydrogel after cervical injection. Study Design: Silk hydrogel (200 μL volume) was injected into the cervix. Controls were either injected with saline or treated with cerclage (5-0 polyethylene terephthalate suture). To study the effect on mechanical properties, the cervix was tested in compression. Biodegradation of the hydrogel was followed over 6 weeks. For biocompatibility, expression levels of proinflammatory mediators were studied. Results: Hydrogel injection resulted in significant tissue augmentation-the cross-sectional area of the cervix increased 46.3 ± 3.0%. The modulus of the uninjected and hydrogel-injected tissues was 3.3 ± 0.7 and 3.2 ± 0.5 kPa at 5-10% strain, respectively (p = 0.8). Histology showed a mild inflammatory response surrounding the hydrogel. Biodegradation of the hydrogel showed 70% volume loss over 6 weeks. Hydrogel-injected tissue showed similar inflammatory response compared with cerclage. Conclusions: In pregnant rabbits, cervical injection of the silk-based hydrogel was biocompatible and naturally degraded. No adverse effects on timing of delivery and pup viability were seen. Silk-based hydrogels show promise for tissue augmentation during pregnancy. Impact Statement This research describes the use of injectable silk-based hydrogel for augmenting cervical tissue in vivo in a pregnant rabbit model. Further preclinical development of the methods and insights described in this article can lead to therapeutic use of this hydrogel as an alternative to cerclage in preterm birth due to cervical insufficiency.
Keywords: cerclage; cervix; in vivo; injectable biomaterial; preterm birth; silk.