Biomedical Engineering Reference
In-Depth Information
the following sections as individual components to
the host response. Following that information, host
response interactions gleaned from animal and
human PEEK explants (of both the bulk implant and
particulate debris) will be considered.
Although both attachment and proliferation of
fibroblasts to UHMWPE were significantly reduced
compared with PEEK and the other materials studied,
there was no significant difference in the adhesion of
osteoblasts to the different materials tested. Simi-
larly, the amounts of DNA synthesized (measuring
cell proliferation) by osteoblasts grown on the
various materials did not vary. The results of this
study suggested that (1) fibroblasts and osteoblasts
responded differently to the materials tested and (2)
PEEK did not appear to deleteriously affect osteo-
blasts and fibroblasts. Subsequently, in 1995, Mor-
rison et al.
[8]
reported on the response of osteoblasts
and fibroblasts to an unknown grade of PEEK using
cell protein, intracellular reduced glutathione (GSH),
leakage of lactate dehydrogenase, and the MTT assay
as indices of cellular cytotoxicity. In contrast to the
slightly cytotoxic and inhibited growth rate of
fibroblasts to the epoxy resin polymer tested in the
study, the PEEK material did not display overt signs
of cytotoxicity. In fact, Morrison et al.
[8]
reported
increased osteoblast cell protein content. Due to this
response, these authors concluded: “PEEK would be
the one [sic] of choice for development of an iso-
elastic implant and, in view of its stimulatory effect
on osteoblast protein content, it may encourage
ingrowth of bone around the prosthesis and thus
minimize joint loosening”
[8]
. A similar cell culture
study using osteoblasts and fibroblasts was con-
ducted using CFR-PEEK
[9]
. The grade of PEEK
used in the study was not described. In this study,
Macnair et al.
[9]
placed special emphasis on char-
acterizing the surface of the PEEK composite, which
was found to be significantly rougher than Ti alloy.
The cellular response to the PEEK composite was
noted to be similar to the results from the study by
Hunter et al.
[7]
.
Scotchford et al.
[10]
examined the in vitro bio-
logical response of human (trabecular bone) osteo-
blasts and murine macrophages to the chopped
CFR-PEEK polymer with the thought that the PEEK-
CFR composite had potential to be used as a total hip
replacement material. CFR-PEEK and titanium alloy
(Ti6Al4V) discs showed no significant difference in
the extent of osteoblast attachment and proliferation.
Markers for bone metabolic activity (alkaline phos-
phatase, Type I collagen production, and osteocalcin)
associated with the PEEK discs were not significantly
different to the Ti6Al4V discs
[10]
. Scotchford et al.
reported that although hydrogen peroxide production
by macrophages was raised on the CFR-PEEK
7.2 Cell Culture and Toxicity
Studies
Considerable scientific evidence currently exists to
support the biocompatibility of PEEK biomaterials
[3,4]
. Williams et al. reported the first animal studies
of PEEK in the literature. Neat PEEK and carbon
fiber-reinforced (CFR) samples produced by Imperial
Chemical Industries (ICI) (including 450G resin)
were subcutaneously implanted in rabbits for
6 months and submuscularly implanted in rats for
30 weeks. Williams et al.
[5]
stated that PEEK elicited
a “minimal response” in both animal models. The first
cell culture cytotoxicity experiments published for
PEEKwere performed byWenz et al.
[6]
usingmurine
fibroblast L929 cells (ATCC #CCL 1) per American
Society for Testing ofMaterials International (ASTM)
standard F813. Both extract and direct contact cell
culture tests using a 30%polyacrylonitrile (PAN) CFR
composite PEEK material (LNP Corporation) were
performed. After 96 h of exposure to PEEK extracts,
the cell cultures were reported as “healthy” and they
“did not appear different than negative controls”
[6]
.
No lysis was observed in the cell cultures adjacent to
the PEEK extracts. In the direct contact experiments
with PEEK, healthy cell monolayers were observed
adjacent to the materials. Based on these results from
the extract and direct contact cell culture tests, the
authors concluded that the PEEK composite exhibited
“excellent” in vitro biocompatibility in the ASTM
standard cell culture models.
The proliferation and attachment of osteoblasts
and fibroblasts to PEEK were evaluated by Hunter
et al.
[7]
in a series of cell culture experiments. 450G
PEEK resin was used as well as Ti alloy, CoCr
alloy, and ultrahigh-molecular-weight polyethylene
(UHMWPE) as controls. Cell lines were obtained
from rat osteogenic sarcoma (osteoblasts), rat-tail
tendon (fibroblasts), and human fetal lung (fibro-
blasts). Proliferation of fibroblasts and osteoblasts
was measured using incorporation of tritiated
thymidine into total DNA. Attachment of cells was
assessed by an image analysis system that measured
the focal adhesion plaque of a component of the cell.
