Autor: |
Ren B; Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University, Munich, Marchioninistr. 15, 81377 Munich, Germany.; Departments of Orthopedics, Zhongnan Hospital of Wuhan University, 430072 Wuhan, China., Betz OB; Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University, Munich, Marchioninistr. 15, 81377 Munich, Germany.; Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA., Seitz D; BioMed Center Innovation gGmbH, 95448 Bayreuth, Germany., Thirion C; Sirion Biotech GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany., Salomon M; Sirion Biotech GmbH, Am Klopferspitz 19, 82152 Martinsried, Germany., Jansson V; Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University, Munich, Marchioninistr. 15, 81377 Munich, Germany., Müller PE; Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University, Munich, Marchioninistr. 15, 81377 Munich, Germany., Betz VM; Department of Orthopedic Surgery, Physical Medicine and Rehabilitation, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University, Munich, Marchioninistr. 15, 81377 Munich, Germany. |
Abstrakt: |
Human adipose-derived stem cells (hADSCs) have the capacity for osteogenic differentiation and, in combination with suitable biomaterials and growth factors, the regeneration of bone defects. In order to differentiate hADSCs into the osteogenic lineage, bone morphogenetic proteins (BMPs) have been proven to be highly effective, especially when expressed locally by route of gene transfer, providing a constant stimulus over an extended period of time. However, the creation of genetically modified hADSCs is laborious and time-consuming, which hinders clinical translation of the approach. Instead, expedited single-surgery gene therapy strategies must be developed. Therefore, in an in vitro experiment, we evaluated a novel growth factor delivery system, comprising adenoviral BMP-2 transduced fascia tissue in terms of BMP-2 release kinetics and osteogenic effects, on hADSCs seeded on an innovative biomimetic spongiosa-like scaffold. As compared to direct BMP-2 transduction of hADSCs or addition of recombinant BMP-2, overexpressing fascia provided a more uniform, constant level of BMP-2 over 30 days. Despite considerably higher BMP-2 peak levels in the comparison groups, delivery by overexpressing fascia led to a strong osteogenic response of hADSCs. The use of BMP-2 transduced fascia in combination with hADSCs may evolve into an expedited single-surgery gene transfer approach to bone repair. |