Molecular Design of a Naturally Derived Hemostatic Sealant with Prolonged Antimicrobial Activity for Repairing...

Hemorrhaging injuries on dynamic internal organs present significant clinical burdens due to their complex nature. To address therapeutic challenges, an injectable, photocrosslinkable, and multifunctional bioadhesive hydrogel comprising methacrylated gelatin (GelMAG), methacrylated dopamine (DMA), and poly(diallyldimethylammonium chloride) (pDDA), named GDP, is engineered. The hydrogel combined underwater adhesion, antimicrobial activity, and hemostatic performance with high elasticity, biomimetic stiffness, and biocompatibility. The GDP hydrogel displayed >200% elongation and ≈50 kPa Young's modulus in tensile tests. The bioadhesive strongly adhered (>40 kPa strength) to skin, outperforming commercial sealants Coseal and Evicel, and could seal various sizes and shapes of injuries created on explanted pig lungs. Broad-spectrum and long-term in vitro antibacterial activity is noted. During in vivo rat liver puncture and tail amputation, GDP achieved significantly reduced blood loss (≈65%) compared to commercial hemostat Surgicel in some cases. In a clinically relevant porcine lung laceration model, GDP sealed large defects and reduced blood loss by 45-55% compared to Surgicel and hemostatic sealant TISSEEL. It also supported enhanced wound closure and tissue regeneration with minimal inflammation. Ultimately, these findings showcased the potential of GDP to act as an elastic, antibacterial, and hemostatic sealant for the repair of multi-dimensional traumatic injuries on soft, dynamic tissues.