title: Delayed minimally invasive injection of allogenic bone marrow stromal cell sheets regenerates large bone defects in an ovine preclinical animal model.
abstract: Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future.
authors.affiliation: Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Berner
authors.affiliation: Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Henkel
authors.affiliation: Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Woodruff
authors.affiliation: Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Steck
authors.affiliation: Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Nerlich
authors.affiliation: Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schuetz
authors.affiliation: Institute of Health and Biomedical Innovation and Medical Engineering Research Facility, Queensland University of Technology, Brisbane, Queensland, Australia; Department of Trauma Surgery, University of Regensburg, Regensburg, Germany dietmar.hutmacher@qut.edu.au.
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Hutmacher
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D001861:Bone Regeneration; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D023421:Models, Animal; D012756:Sheep; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation*; D014184:Transplantation, Homologous
keywords: Allogenic; Bone regeneration; Bone tissue engineering; Cell injection; Large bone defect; Mesenchymal stem cells; Sheep
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