Biomedical Engineering Reference
In-Depth Information
P3HB-based composites, which are of interest in bone tissue engineering,
were found to have an increasing stiffness with an increasing content of hy-
droxyapatite (HA) [93, 94] or tricalcium phosphate (TCP) [95].
3.2
Biocompatibility
Material-tissue interactions are best described by the term biocompatibility.
Generally defined, biocompatibility is “the ability of a material to perform
with an appropriate host response in a specific application” [96]. This implies
thatanymaterialplacedintoabodywillnotbeinertbutwillinteractwith
the tissue. The biological response of a material is basically dependent on
three factors: the material properties, the host characteristics, and the func-
tional demands on the material. Therefore, the biocompatibility of a material
can only be assessed on the basis of its specific host function and has to be
uniquely defined for each application.
Toxicity Testing
P3HB has been found to be an ubiquitous component of the cellular mem-
branes of animals [97]. The resulting presence of relatively large amounts of
low molecular weight P3HB in the human blood, as well as the fact that the
degradation product, 3-hydroxybutyric acid (3HB), is a common metabolite
of all higher living beings, serve as evidence for the nontoxicity of P3HB [20].
Toxicity testing according to USP XXII and ISO 10993 revealed that P3HB
is suited for use as an implant material. The subcutaneous, intraperitoneal,
and intravenous eluate testing did not result in any significant reactions in
rabbits, mice, or guinea pigs, and no febrile reactions were observed during
the pyrogen test. Histocompatibility was demonstrated in the implantation
study in rabbits (Schmitz KP, personal communication).
P3HB did not cause any inflammation in the chorioallantoic membrane of
the developing egg [98]. P3HB-5%3HV was nontoxic in the bacterial biolu-
minescence test over a period of 16 weeks [99]. P3HB-3HV (7%, 14%, 22%
3HV) films were found to elicit only a mild toxic response in the direct con-
tact or agar diffusion tests [100]. However, P3HB-22%3HV extracts in saline
provoked a noticeable hemolytic reaction [101].
Cell Culture Studies
Mouse fibroblast cell-lines are relatively unaffected by small changes in cell
culture conditions and are therefore commonly used to assess and compare
the cell compatibility of biomaterials in vitro. For example, it was reported
thatNIH3T3mousefibroblastsremainedhighlyviableonP3HBandP3HB-
3HV (15%, 28% 3HV) films [102]. In another study, L929 mouse fibroblasts
showed a better viability on P3HB surfaces than on PLLA [94]. A good cell
compatibility of P3HB films has also been concluded from experiments using
