title: Evaluation of photo-crosslinked fibrinogen as a rapid and strong tissue adhesive.
abstract: Tissue adhesives and sealants are commonly used in surgery either as an adjunct to, or replacement for, sutures. Previously, we have shown that fibrinogen can be crosslinked rapidly to give a high-strength bond in the presence of a ruthenium(II) complex, a persulfate and irradiation with visible light, and that the crosslinked fibrinogen is nontoxic to cells in vitro. This approach addresses limitations to current fibrin sealants that typically have relatively slow curing times and low bond strengths. In the present study, we have evaluated the efficacy and safety of this new biological scaffold sealant in various animal models. When placed as solid implants into rats, the crosslinked fibrinogen persisted for at least 8 weeks but was fully resorbed by 18 weeks with minimal inflammatory responses. When used as a tissue adhesive for repair of skin incisions in rats or as an arterial haemostat in pig, the photo-crosslinked fibrinogen sealed tissue or arrested bleeding within 20 s of application. For the skin incisions, the fibrinogen sealant promoted rapid tissue vascularization and cellular infiltration with no adverse foreign body cell generation. New collagen deposition occurred and with time the matrix had remodelled to acquire large mature collagen fiber bundles which were accompanied by maximum regenerated tensile strength. This biomaterial system may find useful applications in surgical procedures where rapid curing and/or high strength tissue sealing is required.
authors.affiliation: CSIRO Livestock Industries, Queensland Bioscience Precinct, St. Lucia 4072, Queensland, Australia.
authors.forename: C M
authors.initials: CM
authors.lastname: Elvin
authors.forename: S J
authors.initials: SJ
authors.lastname: Danon
authors.forename: A G
authors.initials: AG
authors.lastname: Brownlee
authors.forename: J F
authors.initials: JF
authors.lastname: White
authors.forename: M
authors.initials: M
authors.lastname: Hickey
authors.forename: N E
authors.initials: NE
authors.lastname: Liyou
authors.forename: G A
authors.initials: GA
authors.lastname: Edwards
authors.forename: J A M
authors.initials: JA
authors.lastname: Ramshaw
authors.forename: J A
authors.initials: JA
authors.lastname: Werkmeister
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002417:Cattle; D003432:Cross-Linking Reagents / Q000737:chemistry*; D005260:Female; D005340:Fibrinogen / Q000737:chemistry*; D006490:Hemostatics / Q000737:chemistry; D020007:Implants, Experimental; D008027:Light; D008297:Male; D008422:Materials Testing; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013552:Swine; D014014:Tissue Adhesives / Q000737:chemistry*; D014945:Wound Healing
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D006490:Hemostatics; D014014:Tissue Adhesives; D005340:Fibrinogen