Experimental Animal Models for Tissue-Engineered Bone Regeneration - Engineered Bone: Tissue Engineering Intelligence Unit - page 93

antiinflammatory medication to ensure satisfactory pain control in cats and dogs in these
painful procedures. 17
Ethical Considerations
In vivo experiments should only be done when alternative techniques (cell or organ cul-
tures) fail to solve the problem. When experimenting a new design, preliminary assays should
be performed on a small number of animals and models with the lowest morbidity. All the
animal experiments must be done by experienced and specially trained personnel licensed for
animal experimentation. Protocols must be evaluated by an ethics committee and tests must be
performed in accordance with the usual regulations of the country. In order to prevent unnec-
essary animal usage, the scientific community should be informed of negative results in publi-
cations to minimize future repetition of unfruitful experimentation.
Financial Considerations
Models developed in rodents and rabbits are cost-effective and the volume of material to be
tested is not great. A large number of animals can therefore be operated allowing preliminary
studies performance at low expense. Models using medium-sized to large-sized animals are
expensive and are more demanding as far as housing facilities and support staff is concerned.
They are essentially used in preclinical trials.
Technical Limitations
The choice of laboratory animal must take into consideration the ease of handling as well as
feasibility of postoperative care. When a large animal is needed, sheep are preferred over pigs
which are challenging to manipulate and confine. External fixation will also preferably be per-
formed in dogs which are housed in a clean environment.
The choice of the experimental design is conditioned by individual technical skills and
surgical facilities: whereas calvarial defects, subcutaneous, intramuscular and intraperitoneal
implantations in rodents or rabbits can be performed without specific surgical skills and
specialised instrumentation, segmental bone defects, spinal fusions do require surgical experi-
ence and specific equipment. The experimental design must also take into account the physical
characteristics of the biomaterial. Pastes or liquid must be injected in a closed cavity to prevent
leakage (i.e., sealed metaphyseal defects) and particulate or massive materials often require
additional restraints to remain under stable biomechanical conditions. Lastly, the experimental
design must consider the analysing techniques that will be applied and ensure its compatibility
with them (i.e., presence of metallic implants preclude the use of imaging techniques such as
CT or IRM).
Decision Making: Current Animal Models Used in BRM Evaluation
As stated previously one must identify the setting in which experiments are conducted.
Evaluation of a BRM's biofonctionality is independent of its future field of application and is
always performed in the same animal models. On the contrary preclinical evaluations must be
performed in an animal model that reflects a specific human clinical setting.
Preliminary Evaluation of the Biofonctionality of a New Biomaterial
Heterotopic Implantation
Subcutaneous or intramuscular implantations are the gold standards for in vivo evaluation
of biocompatibility as well as osteogenic and osteoinductive potentials. These simple surgical
procedures are mostly performed in rats and lagomorphs for financial reasons and technical
simplicity but have also been described in larger species. The material is usually directly im-
planted in the recipient bed. Culture cells that are not loaded on a vehicle are inoculated in
diffusion chambers prior to implantation. The nucleopore filters of diffusion chambers prevent
invasion of implanted material by host's cells while allowing the diffusion of nutrients and cell