Open AccessSpatial and temporal patterns of bone formation in ectopically pre‐fabricated, autologous cell‐based engineered bone flaps in rabbits
Author(s) -
Scheufler Oliver,
Schaefer Dirk J.,
Jaquiery Claude,
Braccini Alessandra,
Wendt David J.,
Gasser Jürg A.,
Galli Raffaele,
Pierer Gerhard,
Heberer Michael,
Martin Ivan
Publication year - 2008
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00137.x
Subject(s) - biomedical engineering , stromal cell , tissue engineering , scaffold , connective tissue , anatomy , chemistry , materials science , pathology , medicine
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.