Hemostatic Patches Based on Crosslinked Chitosan Films Applied in Interventional Procedures

Abstract

In this study, we manufactured biocompatible hemostatic crosslinked chitosan (CS) patches and analyzed their physicochemical and biological properties for femoral arterial puncture applications. CS is a representative hemostatic material but has some drawbacks, such as swelling, shrinkage, and brittleness. Thus, it was crosslinked via a 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling reaction and a nucleophilic addition reaction with citric acid (CA), glutaraldehyde (GTA), and genipin (GP) to remedy its shortcomings. The CSCA (crosslinked CS with CA/EDC), CSGTA (crosslinked CS with GTA), and CSG (crosslinked CS with GP) films showed low swelling degrees and good mechanical properties (excluding CSCA) compared with those of neat CS films. Additionally, every crosslinked CS film coated with thrombin (TB-CS) showed enhanced hemostatic ability in the whole blood clotting and activated partial thromboplastin time tests. Furthermore, the CSCA, CSGTA, and CSGP were nontoxic in an in vitro cell cytotoxicity test (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay) using L-929 mouse fibroblasts cells.