title: Biological performance of mussel-inspired adhesive in extrahepatic islet transplantation.
abstract: There is significant need for effective medical adhesives that function reliably on wet tissue surfaces with minimal inflammatory insult. To address these performance characteristics, we have generated a synthetic adhesive biomaterial inspired by the protein glues of marine mussels. In-vivo performance was interrogated in a murine model of extrahepatic syngeneic islet transplantation, as an alternative to standard portal administration. The adhesive precursor polymer consisted of a branched poly(ethylene glycol) (PEG) core, whose endgroups were derivatized with catechol, a functional group abundant in mussel adhesive proteins. Under oxidizing conditions, adhesive hydrogels formed in less than 1 min from catechol-derivatized PEG (cPEG) solutions. Upon implantation, the cPEG adhesive elicited minimal acute or chronic inflammatory response in C57BL6 mice, and maintained an intact interface with supporting tissue for up to one year. In-situ cPEG adhesive formation was shown to efficiently immobilize transplanted islets at the epididymal fat pad and external liver surfaces, permitting normoglycemic recovery and graft revascularization. These findings establish the use of synthetic, biologically-inspired adhesives for islet transplantation at extrahepatic sites.
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Brubaker
authors.forename: Hermann
authors.initials: H
authors.lastname: Kissler
authors.forename: Ling-Jia
authors.initials: LJ
authors.lastname: Wang
authors.forename: Dixon B
authors.initials: DB
authors.lastname: Kaufman
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Messersmith
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D049872:Bivalvia / Q000737:chemistry*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D005951:Glucose Tolerance Test; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000295:instrumentation* / Q000379:methods; D008297:Male; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry; D014014:Tissue Adhesives / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D020100:Hydrogels; D014014:Tissue Adhesives; D011092:Polyethylene Glycols