Biomedical Engineering Reference
In-Depth Information
in the United States, have expressed interest in developing more complex laboratory-based
testing methods. The intent is to develop models that are more representative and predic-
tive of in vivo behavior such as organ cultures presenting similar cellular content and
architecture as the host tissue.
The development of bone organ cultures requires the maintenance of three-dimensional
bone explants and their cellular and extracellular content in the laboratory setting
(Jones et al., 2008). In addition to biological content maintenance in vitro, the physiologic-
like maintenance of bone organ cultures has been challenged by difficulties in appro-
priately reproducing physiologic loading conditions in vitro (Jones et al., 2008). Such
difficulties have resulted in the limited use of bone organ culture studies of hard tissue
integration, which requires establishment and maintenance of cultures for long peri-
ods. However, bone organ cultures have been utilized in other research areas such as
the effects of wear particle composition and size in bone inflammatory response (Zhang
et al., 2008).
It is acknowledged that despite the current difficulties and limitations provided by in
vitro cell and organ cultures, developments will soon result in cell and organ cultures
that are more representative of in vivo scenarios. Such developments will expand the in
vitro evaluation of biomaterials beyond safety issues, mimicking in vivo testing conditions
decreasing the time, cost, and regulatory issues concerning animal research protocols.
In Vivo Testing
After in vitro laboratory testing for the general safety of new biomaterials' surfaces, labo-
ratory in vivo models are the next step in biocompatibility testing complexity.
Various animal models and surgical protocols have been utilized to evaluate the host
response to endosseous implants (Coelho et al., 2009). Despite the development of an exten-
sive literature in the field, variations in wound healing and the kinetics of bone healing
due to local physiologic properties of different surgical sites and animal species have not
been sufficiently characterized to enable direct one-to-one comparisons between animal
models or data extrapolation to human clinical scenarios. Nonetheless, animal models are
of vital importance when novel biomaterial design is compared with previously investi-
gated designs of known clinical performance.
The most frequently used animals for dental implant research are rats, rabbits, sheep,
dogs, pigs, and nonhuman primates. Among the attributes taken into consideration to
determine which animal model is most appropriate for a particular research protocol are
site similarity to humans under physiologic and pathologic conditions as well as availabil-
ity of large numbers of specimens over time (Pearce et al., 2007; Lienbschner et al., 2004).
Other considerations include acceptability to the society, cost, availability, age, size (mul-
tiple implant placement for comparison), tolerance to surgery and captivity, housing, and
animal protection acts of different countries (Schimandle et al., 1994). Specific to studies
considering the bone-implant interface, bone macrostructure, microstructure, and mod-
eling/remodeling kinetics should be considered while extrapolating results to humans
(Schimandle et al., 1994).
Because of its relatively low cost, ease of handling, and a substantial number of previ-
ously published data, the rabbit model has been the most utilized for dental implant bone-
implant interface studies. The amount of published work is then followed by research
protocols utilizing dogs (Pearce et al., 2007; Lienbschner et al., 2004). Detailed information
regarding other animal models utilized in bone-implant interface studies can be found
elsewhere (Pearce et al., 2007; Lienbschner et al., 2004).
