title: Ultrasound-mediated gene transfer (sonoporation) in fibrin-based matrices: potential for use in tissue regeneration.
abstract: It has been suggested that gene transfer into donor cells is an efficient and practical means of locally supplying requisite growth factors for applications in tissue regeneration. Here we describe, for the first time, an ultrasound-mediated system that can non-invasively facilitate gene transfer into cells entrapped within fibrin-based matrices. Since ultrasound-mediated gene transfer is enhanced using microbubbles, we compared the efficacy of neutral and cationic forms of these reagents on the ultrasound-stimulated gene transfer process in gel matrices. In doing so we demonstrated the beneficial effects associated with the use of cationic microbubble preparations that interact directly with cells and nucleic acid within matrices. In some cases, gene expression was increased two-fold in gel matrices when cationic microbubbles were compared with neutral microbubbles. In addition, incorporating collagen into fibrin gels yielded a 25-fold increase in gene expression after application of ultrasound to microbubble-containing matrices. We suggest that this novel system may facilitate non-invasive temporal and spatial control of gene transfer in gel-based matrices for the purposes of tissue regeneration.
authors.affiliation: Sonidel Ltd, Dublin, Ireland.
authors.forename: Nikolitsa
authors.initials: N
authors.lastname: Nomikou
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Feichtinger
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Centre, Austrian Cluster for Tissue Regeneration, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.affiliation: Department of Pharmacy and Pharmaceutical Sciences, University of Ulster, Northern Ireland.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: McHale
mesh_terms: D000818:Animals; D019921:Biotinylation / Q000187:drug effects; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D024042:Collagen Type I / Q000494:pharmacology; D018274:Electroporation / Q000379:methods*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005337:Fibrin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018014:Gene Transfer Techniques; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D045423:Microbubbles; D012038:Regeneration / Q000187:drug effects*; D014465:Ultrasonics
chemical_list: D024042:Collagen Type I; D005337:Fibrin; D008156:Luciferases
keywords: collagen; fibrin; gene transfer; microbubbles; sonoporation; tissue engineering