title: A tissue sealant based on reactive multifunctional polyethylene glycol.
abstract: A rapidly gelling synthetic tissue sealant was developed from tetra-succinimidyl and tetra-thiol-derivatized polyethylene glycol (PEG). The two reagents were dissolved in aqueous buffers at 20% (w/v) solids and sprayed on the tissue site, with the use of a sprayer/mixer device. Good adhesion to collagen membranes, PTFE grafts, and carotid artery was observed in vitro. In a burst test on collagen membranes with a 2-mm orifice defect, the gel sustained fluid pressures of 125 +/- 36 mm Hg (n = 18), fivefold greater than capillary blood pressure and one-half that observed in hypertension. On 0.4-mm-diameter puncture defects in PTFE grafts, pressures of 390-490 mm Hg were sustained, and on 0.6-0.9-mm puncture defects in carotid arteries, pressures of 490 to 840 mm Hg were sustained. In vitro data corresponded to results in vivo, where bleeding in rabbit arteries was stopped immediately in five out of six trials. A significant reduction in time to hemostasis and blood loss, compared to controls, was observed. Carotid artery and subcutaneous implant data in rabbits showed that the formula was compatible with biological tissue. Rapid gelling and effective sealing were dependent on the presence of active succinimidyl ester and thiol groups on PEG. HPLC and chemical substitution methods were useful in predicting whether batches of derivatized PEG would perform satisfactorily.
authors.affiliation: Cohesion Technologies, 2500 Faber Place, Palo Alto, California 94303, USA. dwallace@cson.com
authors.forename: D G
authors.initials: DG
authors.lastname: Wallace
authors.forename: G M
authors.initials: GM
authors.lastname: Cruise
authors.forename: W M
authors.initials: WM
authors.lastname: Rhee
authors.forename: J A
authors.initials: JA
authors.lastname: Schroeder
authors.forename: J J
authors.initials: JJ
authors.lastname: Prior
authors.forename: J
authors.initials: J
authors.lastname: Ju
authors.forename: M
authors.initials: M
authors.lastname: Maroney
authors.forename: J
authors.initials: J
authors.lastname: Duronio
authors.forename: M H
authors.initials: MH
authors.lastname: Ngo
authors.forename: T
authors.initials: T
authors.lastname: Estridge
authors.forename: G C
authors.initials: GC
authors.lastname: Coker
mesh_terms: D000269:Adhesives; D000818:Animals; D001807:Blood Vessel Prosthesis; D003094:Collagen / Q000737:chemistry; D004730:Endothelium, Vascular / Q000187:drug effects; D006490:Hemostatics; D020100:Hydrogels / Q000032:analysis*; D066298:In Vitro Techniques; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers; D019736:Prostheses and Implants; D011817:Rabbits; D013552:Swine; D013718:Tensile Strength; D013997:Time Factors; D014783:Viscosity
chemical_list: D000269:Adhesives; D006490:Hemostatics; D020100:Hydrogels; D011108:Polymers; D011092:Polyethylene Glycols; D003094:Collagen