title: Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model.
abstract: The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone) seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step) or only after six weeks of subcutaneous "incubation" (2-step). After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.
authors.affiliation: Clinic for Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, 4031 Basel, Switzerland. alexander.kaempfen@usb.ch.|Institute for Surgical Research and Hospital Management, University Hospital Basel, 4031 Basel, Switzerland. alexander.kaempfen@usb.ch.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kaempfen
authors.affiliation: Institute for Surgical Research and Hospital Management, University Hospital Basel, 4031 Basel, Switzerland. Atanas.Todorovjr@usb.ch.
authors.forename: Atanas
authors.initials: A
authors.lastname: Todorov
authors.affiliation: Institute for Surgical Research and Hospital Management, University Hospital Basel, 4031 Basel, Switzerland. guvens@stanford.edu.
authors.forename: Sinan
authors.initials: S
authors.lastname: Güven
authors.affiliation: Clinic for Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, 4031 Basel, Switzerland. rene.largo@usb.ch.|Institute for Surgical Research and Hospital Management, University Hospital Basel, 4031 Basel, Switzerland. rene.largo@usb.ch.
authors.forename: René D
authors.initials: RD
authors.lastname: Largo
authors.affiliation: Clinic for Oral and Cranio-Maxillofacial Surgery, University Hospital Basel, 4031 Basel, Switzerland. claude.jaquiery@usb.ch.
authors.forename: Claude
authors.initials: C
authors.lastname: Jaquiéry
authors.affiliation: Institute for Surgical Research and Hospital Management, University Hospital Basel, 4031 Basel, Switzerland. arnaud.scherberich@usb.ch.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Scherberich
authors.affiliation: Institute for Surgical Research and Hospital Management, University Hospital Basel, 4031 Basel, Switzerland. ivan.martin@usb.ch.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.affiliation: Clinic for Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, 4031 Basel, Switzerland. dirk.schaefer@usb.ch.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Schaefer
mesh_terms: D000818:Animals; D001862:Bone Resorption; D016025:Bone Transplantation / Q000379:methods*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005269:Femur / Q000098:blood supply* / Q000293:injuries*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011817:Rabbits; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry; D014182:Transplantation, Autologous
keywords: animal model; bone resorption; decellularized bone; osteosynthesis vascularization; tissue engineering