title: Nanobiomechanics of repair bone regenerated by genetically modified mesenchymal stem cells.
abstract: Genetically modified mesenchymal stem cells (MSCs), overexpressing a BMP gene, have been previously shown to be potent inducers of bone regeneration. However, little was known of the chemical and intrinsic nanomechanical properties of this engineered bone. A previous study utilizing microcomputed tomography, back-scattered electron microscopy, energy-dispersive X-ray, nanoindentation, and atomic force microscopy showed that engineered ectopic bone, although similar in chemical composition and topography, demonstrated an elastic modulus range (14.6-22.1 GPa) that was less than that of the native bone (16.6-38.5 GPa). We hypothesized that these results were obtained due to the specific conditions that exist in an intramuscular ectopic implantation site. Here, we implanted MSCs overexpressing BMP-2 gene in an orthotopic site, a nonunion radial bone defect, in mice. The regenerated bone tissue was analyzed using the same methods previously utilized. The samples revealed high similarity between the engineered and native radii in chemical structure and elemental composition. In contrast to the previous study, nanoindentation data showed that, in general, the native bone exhibited a statistically similar elastic modulus values compared to that of the engineered bone, while the hardness was found to be marginally statistically different at 1000 muN and statistically similar at 7000 muN. We hypothesize that external loading, osteogenic cytokines and osteoprogenitors that exist in a fracture site could enhance the maturation of engineered bone derived from BMP-modified MSCs. Further studies should determine whether longer duration periods postimplantation would lead to increased bone adaptation.
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02115, USA.
authors.forename: Kuangshin
authors.initials: K
authors.lastname: Tai
authors.forename: Gadi
authors.initials: G
authors.lastname: Pelled
authors.forename: Dima
authors.initials: D
authors.lastname: Sheyn
authors.forename: Anna
authors.initials: A
authors.lastname: Bershteyn
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.forename: Ilan
authors.initials: I
authors.lastname: Kallai
authors.forename: Yoram
authors.initials: Y
authors.lastname: Zilberman
authors.forename: Christine
authors.initials: C
authors.lastname: Ortiz
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D001861:Bone Regeneration / Q000502:physiology*; D001842:Bone and Bones / Q000503:physiopathology* / Q000601:surgery; D002460:Cell Line; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D013059:Spectrum Analysis, Raman; D023822:Tissue Engineering / Q000379:methods; D015898:Tomography Scanners, X-Ray Computed
chemical_list: D055396:Bone Morphogenetic Protein 2