title: Isocyanate-functional adhesives for biomedical applications. Biocompatibility and feasibility study for vascular closure applications.
abstract: Biodegradable isocyanate-functional adhesives based on poly(ethylene glycol)-adipic acid esters were synthesized, characterized, and evaluated in vitro and in vivo. Two types of formulations, P2TT and P2MT, were developed by functionalization with 2,4-tolylene diisocyanate (TDI) or 4,4'-methylene-bis(phenyl isocyanate) (MDI), respectively, and branching with 1,1,1-trimethylolpropane (TMP). The biocompatibility of the synthesized adhesive formulations was evaluated as per ISO 10993. Cytotoxicity, systemic toxicity, pyrogenicity, genotoxicity (reverse mutation of Salmonella typhimurium and Escherichia coli), hemolysis, intracutaneous reactivity, and delayed-type hypersensitivity were evaluated. All formulations met the requirements of the conducted standard tests. The biological behavior and ability of the adhesive formulations to close an arteriotomy and withstand arterial pressure following partial approximation with a single suture were evaluated in a rat abdominal aorta model. Animals were evaluated at 1, 2, 3, and 4 weeks after surgery. Macroscopic and histopathologic evaluation of explanted arteries suggested that the P2TT formulation had better in vivo performance than the P2MT formulation. Additionally, the P2TT formulation resulted in less tissue reaction than P2MT formulation. To our knowledge, this is the first study demonstrating the potential of this new class of isocyanate-functional degradable adhesives for vascular applications.
authors.affiliation: Surgical Devices R&D, Covidien, North Haven, Connecticut 06473, USA. ahmad.hadba@covidien.com
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Hadba
authors.forename: Nadya
authors.initials: N
authors.lastname: Belcheva
authors.forename: Fatima
authors.initials: F
authors.lastname: Jones
authors.forename: Ferass
authors.initials: F
authors.lastname: Abuzaina
authors.forename: Allison
authors.initials: A
authors.lastname: Calabrese
authors.forename: Mbiya
authors.initials: M
authors.lastname: Kapiamba
authors.forename: Walter
authors.initials: W
authors.lastname: Skalla
authors.forename: Jack L
authors.initials: JL
authors.lastname: Taylor
authors.forename: George
authors.initials: G
authors.lastname: Rodeheaver
authors.forename: John
authors.initials: J
authors.lastname: Kennedy
mesh_terms: D000269:Adhesives / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects*; D005240:Feasibility Studies; D005260:Female; D017953:Isocyanates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008422:Materials Testing; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000269:Adhesives; D001672:Biocompatible Materials; D017953:Isocyanates; D011092:Polyethylene Glycols