title: Development of a gene-activated scaffold platform for tissue engineering applications using chitosan-pDNA nanoparticles on collagen-based scaffolds.
abstract: Biomaterial scaffolds that support cell infiltration and tissue formation can also function as platforms for the delivery of therapeutics such as drugs, proteins, and genes. As burst release of supraphysiological quantities of recombinant proteins can result in adverse side effects, the objective of this study was to explore the potential of a series of collagen-based scaffolds, developed in our laboratory, as gene-activated scaffold platforms with potential in a range of tissue engineering applications. The potential of chitosan, a biocompatible material derived from the shells of crustaceans, as a gene delivery vector was assessed using mesenchymal stem cells (MSCs). A transfection efficiency of >45% is reported which is similar to what is achieved with polyethyleneimine (PEI), a non-viral gold standard vector, without causing cytotoxic side effects. When the optimised chitosan nanoparticles were incorporated into a series of collagen-based scaffolds, sustained transgene expression from MSCs seeded on the scaffolds was maintained for up to 28days and interestingly the composition of the scaffold had an effect on transfection efficiency. These results demonstrate that by simply varying the scaffold composition and the gene (or combinations thereof) chosen; the system has potential for a myriad of therapeutic applications.
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland.
authors.forename: Rosanne M
authors.initials: RM
authors.lastname: Raftery
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland.
authors.forename: Erica G
authors.initials: EG
authors.lastname: Tierney
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Curtin
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Dublin, Ireland; School of Pharmacy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Dublin, Ireland.
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Cryan
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland. Electronic address: fjobrien@rcsi.ie.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D017886:Durapatite / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D006820:Hyaluronic Acid / Q000737:chemistry; D008156:Luciferases / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010957:Plasmids; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D049452:Green Fluorescent Proteins; D006820:Hyaluronic Acid; D003094:Collagen; D004247:DNA; D048271:Chitosan; D017886:Durapatite; D008156:Luciferases
keywords: Chitosan nanoparticles; Gene delivery; Gene-activated scaffold; Mesenchymal stem cells (MSCs); Tissue engineering