title: Hydrophobically-modified chitosan foam: description and hemostatic efficacy.
abstract: BACKGROUND
  Trauma represents a significant public health burden, and hemorrhage alone is responsible for 40% of deaths within the first 24 h after injury. Noncompressible hemorrhage accounts for the majority of hemorrhage-related deaths. Thus, materials which can arrest bleeding rapidly are necessary for improved clinical outcomes. This preliminary study evaluated several self-expanding hydrophobically modified chitosan (HM-CS) foams to determine their efficacy on a noncompressible severe liver injury under resuscitation.
  
  
  METHODS
  Six HM-CS foam formulations (HM-CS1, HM-CS2, HM-CS3, HM-CS4, HM-CS5, and HM-CS6) of different graft types and densities were synthesized, characterized, and packaged into spray canisters using dimethyl ether as the propellant. Expansion profiles of the foams were evaluated in bench testing. Foams were then evaluated in vitro, interaction with blood cells was determined via microscopy, and cytotoxicity was assessed via live-dead cell assay on MCF7 breast cancer cells. For in vivo evaluation, rats underwent a 14 ± 3% hepatectomy. The animals were treated with either: (1) an HM-CS foam formulation, (2) CS foam, and (3) no treatment (NT). All animals were resuscitated with lactated Ringer solution. Survival, total blood loss, mean arterial pressures (MAP), and resuscitation volume were recorded for 60 min.
  
  
  RESULTS
  Microscopy showed blood cells immobilizing into colonies within tight groups of adjacent foam bubbles. HM-CS foam did not display any toxic effects in vitro on MCF7 cells over a 72 h period studied. Application of HM-CS foam after hepatectomy decreased total blood loss (29.3 ± 7.8 mL/kg in HM-CS5 group versus 90.9 ± 20.3 mL/kg in the control group; P <0.001) and improved survival from 0% in controls to 100% in the HM-CS5 group (P <0.001).
  
  
  CONCLUSIONS
  In this model of severe liver injury, spraying HM-CS foams directly on the injured liver surface decreased blood loss and increased survival. HM-CS formulations with the highest levels of hydrophobic modification (HM-CS4 and HM-CS5) resulted in the lowest total blood loss and highest survival rates. This pilot study suggests HM-CS foam may be useful as a hemostatic adjunct or solitary hemostatic intervention.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Dowling
authors.affiliation: Division of Trauma, Acute Care Surgery, and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: William
authors.initials: W
authors.lastname: Smith
authors.affiliation: Division of Trauma, Acute Care Surgery, and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Balogh
authors.affiliation: Division of Trauma, Acute Care Surgery, and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duggan
authors.affiliation: Department of Chemical & Biomolecular Engineering, University of Maryland, College Park, Maryland.
authors.forename: Ian C
authors.initials: IC
authors.lastname: MacIntire
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland.
authors.forename: Erica
authors.initials: E
authors.lastname: Harris
authors.affiliation: Division of Trauma, Acute Care Surgery, and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Tomaz
authors.initials: T
authors.lastname: Mesar
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, Maryland; Department of Chemical & Biomolecular Engineering, University of Maryland, College Park, Maryland.
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Raghavan
authors.affiliation: Division of Trauma, Acute Care Surgery, and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: dking3@partners.org.
authors.forename: David R
authors.initials: DR
authors.lastname: King
mesh_terms: D000818:Animals; D001458:Bandages; D002417:Cattle; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000209:etiology* / Q000628:therapy*; D006490:Hemostatics / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008099:Liver / Q000098:blood supply / Q000293:injuries; D061986:MCF-7 Cells; D008297:Male; D008422:Materials Testing; D010865:Pilot Projects; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D006490:Hemostatics; D048271:Chitosan
keywords: Bleeding; Chitosan; Hemorrhage; Liver; Rat; Spray