title: Spatial and temporal patterns of bone formation in ectopically pre-fabricated, autologous cell-based engineered bone flaps in rabbits.
abstract: Biological substitutes for autologous bone flaps could be generated by combining flap pre-fabrication and bone tissue engineering concepts. Here, we investigated the pattern of neotissue formation within large pre-fabricated engineered bone flaps in rabbits. Bone marrow stromal cells from 12 New Zealand White rabbits were expanded and uniformly seeded in porous hydroxyapatite scaffolds (tapered cylinders, 10-20 mm diameter, 30 mm height) using a perfusion bioreactor. Autologous cell-scaffold constructs were wrapped in a panniculus carnosus flap, covered by a semipermeable membrane and ectopically implanted. Histological analysis, substantiated by magnetic resonance imaging (MRI) and micro-computerized tomography scans, indicated three distinct zones: an outer one, including bone tissue; a middle zone, formed by fibrous connective tissue; and a central zone, essentially necrotic. The depths of connective tissue and of bone ingrowth were consistent at different construct diameters and significantly increased from respectively 3.1+/-0.7 mm and 1.0+/-0.4 mm at 8 weeks to 3.7+/-0.6 mm and 1.4+/-0.6 mm at 12 weeks. Bone formation was found at a maximum depth of 1.8 mm after 12 weeks. Our findings indicate the feasibility of ectopic pre-fabrication of large cell-based engineered bone flaps and prompt for the implementation of strategies to improve construct vascularization, in order to possibly accelerate bone formation towards the core of the grafts.
authors.affiliation: Department of Surgery, University Hospital Basel, Basel, Switzerland. oliver.scheufler@helios-kliniken.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Scheufler
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Schaefer
authors.forename: Claude
authors.initials: C
authors.lastname: Jaquiery
authors.forename: Alessandra
authors.initials: A
authors.lastname: Braccini
authors.forename: David J
authors.initials: DJ
authors.lastname: Wendt
authors.forename: Jürg A
authors.initials: JA
authors.lastname: Gasser
authors.forename: Raffaele
authors.initials: R
authors.lastname: Galli
authors.forename: Gerhard
authors.initials: G
authors.lastname: Pierer
authors.forename: Michael
authors.initials: M
authors.lastname: Heberer
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D018786:Bone Substitutes / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology; D002478:Cells, Cultured; D002516:Ceramics; D003238:Connective Tissue; D020007:Implants, Experimental; D008279:Magnetic Resonance Imaging; D010012:Osteogenesis; D016062:Porosity; D011817:Rabbits; D017154:Stromal Cells / Q000166:cytology; D013997:Time Factors; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014057:Tomography, X-Ray Computed
chemical_list: D018786:Bone Substitutes
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