Decellularized liver extracellular matrix and thrombin loaded biodegradable TOCN/Chitosan nanocomposite for hemostasis and wound healing in rat liver hemorrhage model

Abstract

During deep noncompressible wound management, surgery, transplantation or post-surgical hemorrhage, rapid blood absorption and hemostasis are the key factors to be taken into consideration to reduce unexpected deaths from severe trauma. In this study, a novel hemostatic biodegradable nanocomposite was fabricated where decellularized liver extracellular matrix (L-ECM) was loaded with two natural polymers (oxidized cellulose and chitosan) in association with thrombin. Plant-derived oxidized cellulose nanofiber (TOCN) and Chitosan (CS) from deacylated chitin were self-assembled with each other by electrostatic interactions. ECM was prepared by the whole tissue decellularization process and incorporated into the composite as a source of collagen and other integrated growth factors to promote wound healing. Thrombin was also anchored with the polymers by freeze drying for enhanced hemostatic efficiency of the composite. This study is the first of its kind to report non-solubilized L-ECM and thrombin loaded TOCN and CS composite, CN/CS/EM-Th for faster hemostasis effect in a rat tail amputation (~71s) and liver avulsion model (~41s). Furthermore, excellent liver wound regeneration efficacy was observed in-vivo in comparison to the commercially available oxidized regenerated cellulose product SURGICEL gauge.