title: Reduction of adhesion formation by postoperative administration of ionically cross-linked hyaluronic acid.
abstract: OBJECTIVE
  To examine the efficacy of various formulations of hyaluronic acid (HA), including HA ionically cross-linked with trivalent iron, in animal models of adhesion formation.
  
  
  METHODS
  Hyaluronic acid formulation of varying concentrations and cross-linked densities were prepared and evaluated in a rabbit uterine horn model and a rabbit sidewall model.
  
  
  METHODS
  ETHICON, Inc., Somerville, New Jersey.
  
  
  METHODS
  New Zealand White rabbits.
  
  
  METHODS
  Test formulations were applied as intraperitoneal instillates after surgery.
  
  
  METHODS
  Adhesion formation was assessed at 7 and 14 days (sidewall and uterine horn model, respectively).
  
  
  RESULTS
  Hyaluronic acid that was not ionically cross-linked was ineffective in reducing adhesions in these models even at high viscosity, whereas the ionically cross-linked formulations of HA with trivalent iron were highly effective. Efficacy improved with increased levels of ionic cross-linking. Flowable gels, which could be delivered readily by syringe and cannula, also were effective when administered at a site remote from injury and with saline present.
  
  
  CONCLUSIONS
  Whereas previous studies show that HA was effective in reducing adhesions peripheral to the site of injury, HA ionically cross-linked with trivalent iron was effective in reducing adhesions at all sites. From these studies, a formulation of HA ionically cross-linked with trivalent iron, 0.5% Ferric Hyaluronate Gel (LUBRICOAT; ETHICON, Inc., Somerville, NJ), was identified for subsequent clinical evaluations.
authors.affiliation: Ethicon Inc., Somerville, New Jersey 08876-0151, USA.
authors.forename: D B
authors.initials: DB
authors.lastname: Johns
authors.forename: K E
authors.initials: KE
authors.lastname: Rodgers
authors.forename: W D
authors.initials: WD
authors.lastname: Donahue
authors.forename: T C
authors.initials: TC
authors.lastname: Kiorpes
authors.forename: G S
authors.initials: GS
authors.lastname: diZerega
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007263:Infusions, Parenteral; D007501:Iron / Q000737:chemistry*; D010532:Peritoneal Diseases / Q000209:etiology / Q000517:prevention & control*; D010537:Peritoneum / Q000187:drug effects* / Q000601:surgery; D011184:Postoperative Period; D011817:Rabbits; D000267:Tissue Adhesions / Q000209:etiology / Q000517:prevention & control; D014599:Uterus / Q000187:drug effects* / Q000601:surgery; D014783:Viscosity; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D006820:Hyaluronic Acid; D007501:Iron