Experimental Animal Models for Tissue-Engineered Bone Regeneration - Engineered Bone: Tissue Engineering Intelligence Unit - page 94

contacts through the pores. Intraperitoneal implantation of these chambers is also currently
performed. 18-20
Orthotopic Implantation
Orthotopic implantation allows evaluation of osteoconductivity and osseointegration of
the material as well as its biodegradability in a bony environment.
Rat calvaria is the gold standard model for orthotopic implantation. Calvaria develops from
a membrane precursor, has poor blood supply and a relative deficiency of bone marrow. Calva-
rial defects therefore create a hostile environment for bone healing. Single midsagittal 8 mm
circular defects 2 and bilateral 5 mm parietal defects 21 can be performed in rats: both create
CSD as they give rise to a fibrous nonunion when bone loss is not replaced. Craniotomies are
easy to perform, have low morbidity and are highly reproducible if created with a circular
trephine. All forms of material can be evaluated in that location which is particularly well
suited for granular or paste-like materials (for illustrations see paper by Logeart-Avramoglou).
A large number of animals can be operated on allowing significant statistical analysis. Laterally
performed craniotomies have the advantage of allowing paired design and minimised morbid-
ity while avoiding accidental damage to the midsagittal sinus. The close vicinity of adjacent
defects may nevertheless allow substance diffusion and impair model relevance. 22
Preclinical Evaluations of Augmenting Bone Healing Properties in Bone
Replacement Procedures
Cranial Surgery
Calvarial, parietal or skull defects have been described in rabbit, dog, sheep, minipig and
NHP. 2,3,22,23 They are easy to perform, are highly reproducible and have low morbidity. The
experimental design correctly reflects the clinical setting in which cranioplasty is performed
although calvaria regenerative capacity in animals encompasses that of humans in whom calva-
ria is devoid of muscular insertions. Several defects can be performed in the same animal allow-
ing comparisons of several biomaterials, and negative and positive controls in the same animal.
Up to twelve 22-mm defects per animal have for example been performed by Viljanen in
sheep. 22
Maxillo-Facial Surgery
Filling Defects
Filling defects in maxillofacial surgery often result from alveolar bone resorption at tooth
extraction sites. Such models have been developed in the dog by mandibular and maxillary
premolar extractions. 24 Bone fillers are also currently evaluated in uni or bicortical mandibular
filling defects, developed in the dog, 3 miniature pig, 25 and sheep. 7 Mandibular defects have
several advantages over periodontal wounds: 7 (i) they can be standardised in size and shape, (ii)
they involve a closed wound rather than an open wound in the mouth, (iii) the only tissue
regenerated is bone. Calvarial defects like those described in rabbits, dogs and NHP are also
currently used because of anatomic similarities with the mandible (two cortical plates with
intervening cancellous bone). 2 A nasal critical-size defect has been described in large size Sprague
Dawley rats. 26 The later has the advantage of having been developed in an endochondral type
bone whereas calvarial defects are developed in a membranous type bone.
Segmental Bone Defects
Mandibular discontinuity defects are created for experimental trials to mimic segmental
bone resections that are currently performed in oncologic maxillofacial surgery. These designs
partly reproduce the adverse clinical setting in which bone replacement usually takes place in
maxillofacial surgery: (i) bone loading requires segment motion neutralisation by additional
bone fixation when extensive bone resection is performed, (ii) replacement is performed in the