title: Biodegradable poly (lactic acid-co-glycolic acid) scaffolds as carriers for genetically-modified fibroblasts.
abstract: Recent advances in gene delivery into cells allow improved therapeutic effects in gene therapy trials. To increase the bioavailability of applied cells, it is of great interest that transfected cells remain at the application site and systemic spread is minimized. In this study, we tested clinically used biodegradable poly(lactic acid-co-glycolic acid) (PLGA) scaffolds (Vicryl & Ethisorb) as transient carriers for genetically modified cells. To this aim, we used human fibroblasts and examined attachment and proliferation of untransfected cells on the scaffolds in vitro, as well as the mechanical properties of the scaffolds at four time points (1, 3, 6 and 9 days) of cultivation. Furthermore, the adherence of cells transfected with green fluorescent protein (GFP) and vascular endothelial growth factor (VEGF165) and also VEGF165 protein secretion were investigated. Our results show that human fibroblasts adhere on both types of PLGA scaffolds. However, proliferation and transgene expression capacity were higher on Ethisorb scaffolds most probably due to a different architecture of the scaffold. Additionally, cultivation of the cells on the scaffolds did not alter their biomechanical properties. The results of this investigation could be potentially exploited in therapeutic regiments with areal delivery of transiently transfected cells and may open the way for a variety of applications of cell-based gene therapy, tissue engineering and regenerative medicine.
authors.affiliation: Experimental Plastic Surgery, Department for Plastic Surgery and Hand Surgery, Klinikum rechts der Isar, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Perisic
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics and Sportsorthopaedics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Foehr
authors.affiliation: Experimental Plastic Surgery, Department for Plastic Surgery and Hand Surgery, Klinikum rechts der Isar, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Hopfner
authors.affiliation: Experimental Plastic Surgery, Department for Plastic Surgery and Hand Surgery, Klinikum rechts der Isar, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Klutz
authors.affiliation: Department of Orthopaedics and Sportsorthopaedics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Burgkart
authors.affiliation: Experimental Plastic Surgery, Department for Plastic Surgery and Hand Surgery, Klinikum rechts der Isar, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Alexei
authors.initials: A
authors.lastname: Slobodianski
authors.affiliation: Johnson & Johnson MEDICAL GmbH, Norderstedt, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Goeldner
authors.affiliation: Experimental Plastic Surgery, Department for Plastic Surgery and Hand Surgery, Klinikum rechts der Isar, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Machens
authors.affiliation: Experimental Plastic Surgery, Department for Plastic Surgery and Hand Surgery, Klinikum rechts der Isar, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Klinik für Unfallchirurgie, Orthopädie und Plastische Chirurgie, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Arndt F
authors.initials: AF
authors.lastname: Schilling
mesh_terms: D002448:Cell Adhesion; D060846:Cell Engineering; D002460:Cell Line; D049109:Cell Proliferation; D005347:Fibroblasts / Q000502:physiology*; D005818:Genetic Engineering; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid