Reduction of adhesion formation by postoperative administration of ionically cross-linked hyaluronic acid.
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.
Johns
D B
DB
Ethicon Inc., Somerville, New Jersey 08876-0151, USA.
Rodgers
K E
KE
Donahue
W D
WD
Kiorpes
T C
TC
diZerega
G S
GS
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*
D006820:Hyaluronic Acid; D007501:Iron