Bioadhesive, Hemostatic, and Antibacterial <i>in Situ</i> Chitin–Fibrin Nanocomposite Gel for Controlling Bleeding and Preventing Infections at Mediastinum

Abstract

Mediastinitis occurs after cardiac surgery and is a major threat to patient’s life due to postoperative bleeding and deep sternal wound infection. Major challenge in treating this condition is that it demands a material that should adhere to the applied site and act as both a hemostatic and an antibacterial agent. On the basis of this we have developed an in situ forming tissue adhesive chitin–fibrin (CH-FB) gel with tigecycline loaded gelatin nanoparticles (tGNPs) for controlling bleeding and preventing bacterial infection. Spherical shaped tGNPs (231 ± 20 nm) were prepared and characterized. In situ forming tGNPsCH-FB gel was formed using a dual syringe applicator in which one syringe was loaded with a mixer of fibrinogen solution, chitin gel, and tGNPs; the other syringe was loaded with a mixture of thrombin solution, chitin gel, and tGNPs. Both these mixtures were injected together. In situ gel formed within a minute and exhibited excellent tissue adhesive property. tGNPsCH-FB gel was found to be cyto-compatible against human umbilical vein endothelial cells (HUVECs). Sustained release of tigecycline from tGNPsCH-FB gel was found to occur over 21 days. In vitro antibacterial activity of tGNPsCH-FB gel was tested against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (E. coli), and their clinical isolates. Furthermore, in vivo hemostatic potential of tGNPsCH-FB gel was evaluated in deep organ injuries created in Sprague–Dawley rats. The developed gel exhibited rapid blood clotting potential by achieving hemostasis within 154 and 84 s under femoral artery (pressured) and liver (oozing) bleeding conditions. Hence, these findings exhibit the potential application of the developed tGNPsCH-FB gel to adhere at surgical site for controlling bleeding and prevent bacterial infection after cardiac surgery.