Peri-prosthetic bone
resorption and loosening of artificial joints
have been widely recognized to limit the performance of the load-bearing
implants. Therefore, the present study probes into the cyto-, hemo-,
and histocompatibility of the small sized wear particulates of ZrO2-toughened Al2O3 (ZTA). In order to
develop a comprehensive, yet clinically relevant understanding, a
comparison is made with two baseline ceramics (Al2O3 and ZrO2) and metallic material (CoCr), all in
particulate forms. While in vitro cytotoxicity
assessment was carried out with mouse osteoblast cells, preclinical
testing of intra-articularly injected particulates up to the concentration
25 wt % in PBS over the period of 12 weeks was performed in mouse
model. Interestingly, mouse osteoblast cells, cultured in media with
ZTA, Al2O3, and ZrO2 particulates
of three different concentrations (0.25, 2.5, and 25 mg/mL) exhibited
uncompromised cell viability and considerable cell spreading, up to
the time frame of 72 h. In contrast, similar experiments with CoCr
particulates demonstrated significant decrease in cellular growth
with drastic change in osteoblast proliferation behavior. Furthermore,
the decrease in RBC damage after contact with ZTA, Al2O3, and ZrO2 particulates at 25 mg/mL of dose level
illustrated 4.4, 5.8, and 1.25% hemolysis, respectively, confirming
clinically acceptable hemocompatibility. However, hematic activity
of CoCr particles was reflected with 15.6% of hemolysis. In
vivo, the absence of any significant effect of intra-articularly
injected ceramic (Al2O3, ZrO2, ZTA)
as well as metallic (CoCr) particulates on complete hemogram and serum
biochemistry of Balb/C mice was recorded at all the time points up
to 12 weeks. The extensive histological analysis confirmed the absence
of any signature of the tissue-level toxicity at all time points.
The pro-inflammatory cytokine analysis using TNF-α and IL-1β
markers provided complementary evidence toward nongranulomatous and
nonimmunogenic response of synovial membrane of knee joint and other
vital organs of mice that were exposed to Al2O3, ZrO2, ZTA, and CoCr particulates. Taken together, our
results establish the nontoxic nature of oxide ceramic particulates
to bone cells, in vitro, as well as to periprosthetic
tissue, in vivo.