title: Ruthenium-catalyzed photo cross-linking of fibrin-based engineered tissue.
abstract: Most cross-linking methods utilize chemistry or physical processes that are detrimental to cells and tissue development. Those that are not as harmful often do not provide a level of strength that ultimately meets the required application. The purpose of this work was to investigate the use of a ruthenium-sodium persulfate cross-linking system to form dityrosine in fibrin-based engineered tissue. By utilizing the tyrosine residues inherent to fibrin and cell-deposited proteins, at least 3-fold mechanical strength increases and 10-fold stiffness increases were achieved after cross-linking. This strengthening and stiffening effect was found to increase with culture duration prior to cross-linking such that physiologically relevant properties were obtained. Fibrin was not required for this effect as demonstrated by testing with collagen-based engineered tissue. Cross-linked tissues were implanted subcutaneously and shown to have minimal inflammation after 30 days, similar to non-cross-linked controls. Overall, the method employed is rapid, non-toxic, minimally inflammatory, and is capable of increasing strength and stiffness of engineered tissues to physiological levels.
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, 7-105 Nils Hasselmo Hall, 312 Church St., Minneapolis, MN 55455, United States.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Bjork
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Johnson
authors.forename: Robert T
authors.initials: RT
authors.lastname: Tranquillo
mesh_terms: D000818:Animals; D002384:Catalysis / Q000187:drug effects / Q000528:radiation effects; D002452:Cell Count; D003094:Collagen / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005337:Fibrin / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020007:Implants, Experimental; D008027:Light; D055595:Mechanical Phenomena / Q000187:drug effects / Q000528:radiation effects; D008855:Microscopy, Electron, Scanning; D051381:Rats; D012428:Ruthenium / Q000494:pharmacology*; D040521:Subcutaneous Tissue / Q000187:drug effects; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D014357:Trypsin / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D012428:Ruthenium; D005337:Fibrin; D005340:Fibrinogen; D003094:Collagen; D014357:Trypsin