title: A self-assembling hydrophobically modified chitosan capable of reversible hemostatic action.
abstract: Blood loss at the site of a wound in mammals is curtailed by the rapid formation of a hemostatic plug, i.e., a self-assembled network of the protein, fibrin that locally transforms liquid blood into a gelled clot. Here, we report an amphiphilic biopolymer that exhibits a similar ability to rapidly gel blood; moreover, the self-assembly underlying the gelation readily allows for reversibility back into the liquid state via introduction of a sugar-based supramolecule. The biopolymer is a hydrophobically modified (hm) derivative of the polysaccharide, chitosan. When hm-chitosan is contacted with heparinized human blood, it rapidly transforms the liquid into an elastic gel. In contrast, the native chitosan (without hydrophobes) does not gel blood. Gelation occurs because the hydrophobes on hm-chitosan insert into the membranes of blood cells and thereby connect the cells into a sample-spanning network. Gelation is reversed by the addition of α-cyclodextrin, a supramolecule having an inner hydrophobic pocket: polymer hydrophobes unbind from blood cells and embed within the cyclodextrins, thereby disrupting the cell network. We believe that hm-chitosan has the potential to serve as an effective, yet low-cost hemostatic dressing for use by trauma centers and the military. Preliminary tests with small and large animal injury models show its increased efficacy at achieving hemostasis - e.g., a 90% reduction in bleeding time over controls for femoral vein transections in a rat model.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA. mdowlin2@umd.edu
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Dowling
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Mark A
authors.initials: MA
authors.lastname: Keibler
authors.forename: John R
authors.initials: JR
authors.lastname: Hess
authors.forename: Grant V
authors.initials: GV
authors.lastname: Bochicchio
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Raghavan
mesh_terms: D000328:Adult; D000818:Animals; D001704:Biopolymers / Q000737:chemistry / Q000627:therapeutic use; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D003505:Cyclodextrins / Q000737:chemistry; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006490:Hemostatics / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D013552:Swine; D055815:Young Adult
chemical_list: D001704:Biopolymers; D003505:Cyclodextrins; D006490:Hemostatics; D048271:Chitosan