Biomedical Engineering Reference
In-Depth Information
Repeated haemocompatibility studies have been performed to evaluate possible reactions in
whole human blood as a result of contact with Ca-aluminate materials (Axen et al 2004).
Test items were an experimental Ca-aluminate based material and Xeraspine,
Vertebroplastic and Norian (Calcium Phosphate Cement, Synthes Inc). A Chandler loop
model was used in which circulating human blood was in contact with the test materials for
up to 4 hours. For comparison, loops free from test materials were used. Platelet count
(PLT), thrombin-antithrombin (TAT) complex, complement factors C3a and C5b-9 (TCC),
and TNF-α were assayed. The degree of haemolysis was assessed by the Drabkin method.
Norian (a calcium phosphate based material) invariably induced extensive clotting already
after 60 minutes, verified macroscopically and also by significantly reduced PLT in
comparison to the Control loops, whereas there was no significant reduction in PLT in the
loops with Ca-alumiante material or Vertebroplastic, respectively, neither at 60 nor at 240
minutes. The Ca-aluminate material did not induce haemolysis to a greater extent than any
of the other materials tested. TCC was activated to a certain degree by the biomaterial,
comparable to what is commonly observed for artificial materials. TNF-α generation,
indicative of activation of white blood cells, was not enhanced by either Vertobroplastic or
the Ca-aluminate material.
Based on all above mentioned data and generated toxicity data, it is considered that there is
no reason to expect that the Ca-aluminate biomaterials when used in accordance with the
intended clinical use will create any adverse effects. The Ca-aluminate based materials fulfill
the requirements of the harmonized standard ISO 10993:2003.
3.1.1.1 Complementary reactions of Ca-aluminate in presence of body liquid.
Complementary reactions occur when the Ca-aluminate is in contact with tissue containing
body liquid. Several mechanisms have been identified, which control how the Ca-aluminate
material is integrated onto tissue. These mechanisms affect the integration differently
depending on what type of tissue the biomaterial is in contact with, and in what state (un-
hydrated or hydrated) the CA is introduced. These mechanisms are summarized as follows
and described in more details elsewhere (Hermansson, 2009);
Mechanism 1: Main reaction, the hydration step of CAC (Eq. 1 above)
Mechanism 2: Apatite formation in presence of phosphate ions in the
biomaterial
Mechanism 3: Apatite formation in the contact zone in presence of body liquid
Mechanism 4: Transformation of hydrated Ca-aluminate into apatite and
gibbsite
Mechanism 5: Biological induced integration and ingrowth, i.e. bone formation
at the contact zone
Mechanism 6: Point-welding due to mass increase when in contact with body
liquid.
When phosphate ions or water soluble phosphate compounds are present in the biomaterial
(powder or liquid) an apatite formation occurs according to the reaction
5Ca
2+
+
3
PO
4
3-
+ OH
-
Ca
5
(PO
4
)
3
OH
This complementary reaction to the main reaction occurs due to the presence of Ca-ions and
a basic (OH
-
) environment created by the Ca-aluminate material. The solubility product of
apatite is very small [Ks = 10
-58
], so apatite is easily precipitated. Body liquid contains
among others the following ions HPO
4
2-
and H
2
PO
4
-
.
In contact with the Ca-aluminate
