title: Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model.
abstract: New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 μg/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in order to engineer an axially vascularized primary stable bone replacement in clinically relevant size for free transplantation.
authors.affiliation: 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
authors.affiliation: 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: Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg FAU, Erlangen, Germany.
authors.forename: Gloria
authors.initials: G
authors.lastname: Deschler
authors.affiliation: Institute of Physics, University of Rostock, Rostock, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gerber
authors.affiliation: Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg FAU, Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Arkudas
authors.affiliation: Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich-Alexander-University of Erlangen-Nürnberg FAU, Erlangen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kneser
authors.affiliation: 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: 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
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology*; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D053761:Nanocomposites / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D044967:Serum / Q000502:physiology*; D012756:Sheep; D012822:Silicon Dioxide / Q000737:chemistry*; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D004337:Drug Carriers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D012822:Silicon Dioxide
keywords: autologous serum; bone tissue engineering; mesenchymal stem cells; nanostructured bone substitute; recombinant human bone morphogenetic protein 2; sheep model