title: Bone Tissue Engineering Under Xenogeneic-Free Conditions in a Large Animal Model as a Basis for Early Clinical Applicability.
abstract: For decades, researchers have been developing a range of promising strategies in bone tissue engineering with the aim of producing a significant clinical benefit over existing therapies. However, a major problem concerns the traditional use of xenogeneic substances for the expansion of cells, which complicates direct clinical transfer. The study's aim was to establish a totally autologous sheep model as a basis for further preclinical studies and future clinical application. Ovine mesenchymal stromal cells (MSC) were cultivated in different concentrations (0%, 2%, 5%, 10%, and 25%) of either autologous serum (AS) or fetal calf serum (FCS). With an increase of serum concentration, enhanced metabolic activity and proliferation could be observed. There were minor differences between MSC cultivated in AS or FCS, comparing gene and protein expression of osteogenic and stem cell markers, morphology, and osteogenic differentiation. MSC implanted subcutaneously in the sheep model, together with a nanostructured bone substitute, either in stable block or moldable putty form, induced similar vascularization and remodeling of the bone substitute irrespective of cultivation of MSC in AS or FCS and osteogenic differentiation. The bone substitute in block form together with MSC proved particularly advantageous in the induction of ectopic bone formation compared to the cell-free control and putty form. It could be demonstrated that AS is suitable for replacement of FCS for cultivation of ovine MSC for bone tissue engineering purposes. Substantial progress has been made in the development of a strictly xenogeneic-free preclinical animal model to bring future clinical application of bone tissue engineering strategies within reach.
authors.affiliation: 1 Laboratory for Tissue Engineering and Regenerative Medicine, Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg (FAU) , Erlangen, Germany .
authors.forename: Annika
authors.initials: A
authors.lastname: Weigand
authors.affiliation: 1 Laboratory for Tissue Engineering and Regenerative Medicine, Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg (FAU) , Erlangen, Germany .
authors.forename: Justus P
authors.initials: JP
authors.lastname: Beier
authors.affiliation: 1 Laboratory for Tissue Engineering and Regenerative Medicine, Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg (FAU) , Erlangen, Germany .
authors.forename: Rafael
authors.initials: R
authors.lastname: Schmid
authors.affiliation: 1 Laboratory for Tissue Engineering and Regenerative Medicine, Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg (FAU) , Erlangen, Germany .
authors.forename: Tobias
authors.initials: T
authors.lastname: Knorr
authors.affiliation: 1 Laboratory for Tissue Engineering and Regenerative Medicine, Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg (FAU) , Erlangen, Germany .
authors.forename: David
authors.initials: D
authors.lastname: Kilian
authors.affiliation: 1 Laboratory for Tissue Engineering and Regenerative Medicine, Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg (FAU) , Erlangen, Germany .
authors.forename: Rebekka
authors.initials: R
authors.lastname: Götzl
authors.affiliation: 2 Institute of Physics, University of Rostock , Rostock, Germany .
authors.forename: Thomas
authors.initials: T
authors.lastname: Gerber
authors.affiliation: 1 Laboratory for Tissue Engineering and Regenerative Medicine, Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg (FAU) , Erlangen, Germany .
authors.forename: Raymund E
authors.initials: RE
authors.lastname: Horch
authors.affiliation: 1 Laboratory for Tissue Engineering and Regenerative Medicine, Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander University of Erlangen-Nürnberg (FAU) , Erlangen, Germany .
authors.forename: Anja M
authors.initials: AM
authors.lastname: Boos
mesh_terms: D000818:Animals; D064592:Autografts; D018786:Bone Substitutes; D049109:Cell Proliferation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis; D012756:Sheep; D023822:Tissue Engineering
chemical_list: D018786:Bone Substitutes
keywords: bone tissue engineering; large animal model; mesenchymal stem cells; nanostructured scaffolds; osteogenic differentiation; xenogeneic-free