Chlorocatechol-functionalized gelatin nanoparticles as a hemostatic agent with antimicrobial properties

Abstract

Hemorrhage is one of the leading preventable causes of death associated with trauma, which is often complicated by wound infection. Current hemostatic materials are not ideal and lack antimicrobial properties needed for infection prevention. Here, we tested the feasibility for 6-chlorodopamine-functionalized gelatin (GDC) nanoparticles to function as a hemostatic powder with strong tissue adhesion and antibacterial properties. 6-Chlorodopamine contains a catechol sidechain that is further modified with an electron withdrawing chlorine atom, and provides strong tissue adhesion and antimicrobial property. These gelatin nanoparticles are not covalently crosslinked, which enablde them to rapidly transition into an adhesive film when hydrated with an aqueous solution or blood. The chlorination of catechol significantly increased structural integrity, interfacial bonding to tissue surface, and the rate of film formation. Additionally, GDC nanoparticles are noncytotoxic and nonhemolytic, and effectively killed Gram-positive (Staphylococcus epidermidis, Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Finally, GDC nanoparticles achieved significantly faster hemostasis and reduced blood loss when compared to a commercial fibrin glue, Tisseel, in tail transection and liver hemorrhage models performed in mice. These findings highlight the potential of GDC nanoparticle as a versatile, multifunctional hemostatic agent capable of both rapid hemorrhage control and infection prevention. STATEMENT OF SIGNIFICANCE: Existing hemostatic agents often lack effective antimicrobial properties and may not be suited for application in a prehospital setting. This work evaluated a multifunctional, hemostatic nanoparticle that addresses key challenges in hemorrhage control and infection prevention, through a simple, bioinspired formulation. Gelatin nanoparticles were functionalized with chlorocatechol (GDC) that can rapidly transition into adhesive films when hydrated with blood. Chlorocatechol imparted the nanoparticles with strong tissue adhesion, film integrity, and antimicrobial property. In mouse hemorrhage models, GDC significantly reduced blood loss and bleeding time when compared to a commercial fibrin sealant. This powder-form material requires no mixing or specialized equipment to deploy, which makes it potentially suitable for application in a prehospital setting.

Keywords: Antibacterial; Bioadhesive; Chlorocatechol; Hemostatic nanoparticles.