Hemostatic B-knob-triggered microgels (BK-TriGs) to address bleeding in neonates.

Abstract

Hemostatic immaturity in neonates presents critical challenges, especially during surgery, where bleeding and thrombosis risks are elevated. Current treatments rely on transfusing adult blood products, which may cause complications resulting from structural and functional differences between neonatal and adult fibrinogen. To address this, we developed hemostatic B-knob-triggered microgels (BK-TriGs) that target and bridge fibrinogen hole b sites. Functionalized with a fibrin hole b-specific peptide, BK-TriGs enhance clot density and resistance to degradation. In vitro studies using neonatal platelet-poor plasma (PPP) showed that at an optimal concentration, BK-TriGs increased clot density by more than 100% and improved stability by reducing fibrinolysis. Under flow conditions, BK-TriGs promoted robust clot formation compared to plasma-only controls. In an in vivo fib-null (Fga-/-) mouse model transfused with neonatal fibrinogen, BK-TriGs reduced blood loss by 50 to 60% and enhanced fibrin deposition at wound sites. This targeted approach offers a safer, more effective hemostatic solution tailored to neonatal clotting needs.