title: A perfusion bioreactor system efficiently generates cell-loaded bone substitute materials for addressing critical size bone defects.
abstract: Critical size bone defects and non-union fractions are still challenging to treat. Cell-loaded bone substitutes have shown improved bone ingrowth and bone formation. However, a lack of methods for homogenously colonizing scaffolds limits the maximum volume of bone grafts. Additionally, therapy robustness is impaired by heterogeneous cell populations after graft generation. Our aim was to establish a technology for generating grafts with a size of 10.5 mm in diameter and 25 mm of height, and thus for grafts suited for treatment of critical size bone defects. Therefore, a novel tailor-made bioreactor system was developed, allowing standardized flow conditions in a porous poly(L-lactide-co-caprolactone) material. Scaffolds were seeded with primary human mesenchymal stem cells derived from four different donors. In contrast to static experimental conditions, homogenous cell distributions were accomplished under dynamic culture. Additionally, culture in the bioreactor system allowed the induction of osteogenic lineage commitment after one week of culture without addition of soluble factors. This was demonstrated by quantitative analysis of calcification and gene expression markers related to osteogenic lineage. In conclusion, the novel bioreactor technology allows efficient and standardized conditions for generating bone substitutes that are suitable for the treatment of critical size defects in humans.
authors.affiliation: Institute for Interfacial Process Engineering and Plasma Technology IGVP, University of Stuttgart, Stuttgart, Germany.|Department of Orthopedics, Medical University Graz, Graz, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kleinhans
authors.affiliation: Chair Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.|Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany Department.
authors.forename: Ramkumar Ramani
authors.initials: RR
authors.lastname: Mohan
authors.affiliation: Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany Department.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Vacun
authors.affiliation: Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany Department.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz
authors.affiliation: FH Esslingen, Esslingen am Neckar, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Haller
authors.affiliation: Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Institute for Interfacial Process Engineering and Plasma Technology IGVP, University of Stuttgart, Stuttgart, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kahlig
authors.affiliation: Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany Department.
authors.forename: Petra
authors.initials: P
authors.lastname: Kluger
authors.affiliation: Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Finne-Wistrand
authors.affiliation: Chair Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany.|Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany Department.
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.affiliation: Chair Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany. Jan.Hansmann@uni-wuerzburg.de.|Fraunhofer Institute for Interfacial Engineering and Biotechnology, Stuttgart, Germany Department. Jan.Hansmann@uni-wuerzburg.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Hansmann
mesh_terms: D019149:Bioreactors; D018786:Bone Substitutes / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010477:Perfusion / Q000379:methods*; D011091:Polyesters; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D018786:Bone Substitutes; D011091:Polyesters; C550605:poly(lactic acid-co-epsilon-caprolactone)
keywords: Bone substitute; Critical size defect; Perfusion bioreactor system; Poly(LLA-co-CL) scaffold; Tissue engineering