Poster CC6 - HYACINTH: A HYdrogel-based, Adhesive, Contraction-INductive, Therapeutic Hemostatic Material for Postpartum Hemorrhage

Introduction: Postpartum hemorrhage (PPH) is a life-threatening childbirth complication affecting up to 6% of deliveries annually and is the leading cause of maternal morbidity and mortality worldwide (Evensen 2017). The vast majority of cases occur within 24 hours of childbirth and are most often attributed to uterine atony. In this pathologic condition, the uterus is unable to contract against bleeding vessels (Wormer 2022) and requires physical, pharmacologic, or surgical intervention. Oxytocin is the gold standard treatment (Escobar 2022); however, prolonged exposure desensitizes the uterine tissues (Vrachnis 2011). This necessitates alternative strategies to control severe bleeding within the uterus. Our previous nanocomposite hydrogel promotes blood clotting (Gaharwar 2014), but postpartum physiology poses challenges of high blood flow rates. We aim to augment this hydrogel with wet-tissue adhesion and uterotonic drug release to develop a HYdrogel-based, Adhesive, Contraction-INductive, Therapeutic Hemostatic material (“HYACINTH”) capable of addressing the symptoms and underlying cause of PPH.

Materials and

Methods: HYACINTH is fabricated by modifying our previous gelatin-nanosilicate hydrogel (Gaharwar 2014). Conjugation of catechol-containing dopamine to gelatin lends wet tissue adhesivity. Adhesion is assessed in tack, burst strength, lap shear, and submerged adhesion testing. Rheology and mechanical force measurements are used to characterize the injectability of the resulting adhesive hydrogel. Nanosilicates are loaded with uterotonic misoprostol (Gibbins 2013) and the release profile is quantified and compared to clinical dosing regimens. Hemostatic assays confirm procoagulant activity, both in static and dynamic scenarios. Uterotonic ability will be studied in vitro with myometrial cells and tissue strips to support the use in resolving uterine atony.

Results, Conclusions, and Discussions: Preliminary results show successful dopamine addition and dry adhesion. Injectability is maintained with power law indices less than 1 to indicate a shear-thinning fluid and forces less than 30 N for rates up to 20 mL/min. Viscosity decreases with increasing temperature to allow for smooth hydrogel flow into a uterine cavity. A modified tack test demonstrates improved adhesion at body temperature. A model drug (alizarin red) demonstrates sustained release over 72 hours. Clotting time is consistent between HYACINTH and the unmodified hydrogel. Future results will validate HYACINTH under wet conditions, with a burst strength of at least 200 mmHg to withstand physiological blood pressure. HYACINTH can also fill irregular cavities and an ex vivo model will demonstrate the use case. HYACINTH poses strong potential as a multimodal material by addressing both the symptoms (i.e., hemorrhage) and underlying cause (i.e., uterine atony) of PPH. Further work will optimize adhesion with hemostasis and drug release. Ultimately, we aim to develop a material to reduce both immediate mortality and long-term morbidities in postpartum maternal care.

Acknowledgements (Optional): SEH acknowledges a predoctoral fellowship from the American Heart Association (24PRE1200460). The authors thank Dr. Hector O. Chapa, MD, FACOG for his clinical insights and guidance.