Biomedical Engineering Reference
In-Depth Information
groups from phosphoproteins attached to the collagen. The molecular periodicity of the func-
tional groups serves to nucleate the mineral phase heterogeneously. The nucleation of the
thin, plate-like apatite crystals of bone occurs within the discrete spaces within the collagen
fibrils, thereby limiting the possible primary growth of the mineral crystals and forcing them
to be discrete and discontinuous. Only one phase of calcium phosphate is nucleated during
normal, nonpathological mineralization processes (carbonated apatite), and the minerals grow
with a specific crystalline orientation. In biomimetic ceramics, the calcium phosphate stimu-
lates bone healing best when used in the form of nanometer-sized crystals rather than large
crystals that are fused together by the application of high temperatures.
5.4 TISSUE-BIOMATERIAL INTERACTIONS
5.4.1 Interactions with Blood and Proteins
The implantation of a biomaterial often creates a wound, and bleeding generally ensues.
Blood thus typically makes first contact with the implanted biomaterial. Blood is a mixture
of water, various kinds of cells and cell fragments (platelets), salts, and proteins (plasma).
Proteins play an important role in determining the biological activity of the tissue-implant
interface. Biomaterials can promote cell/tissue attachment and activity by allowing selec-
tive protein adsorption or can inhibit tissue interactions by repelling protein. Most impor-
tantly, changes in the microenvironment that can occur after biomaterial implantation,
such as changes to pH and ionic strength, can alter the conformation of a nearby protein
and thus its function. Proteins also can experience structural alterations during interaction
with the solid surfaces of biomaterials and lose some of their biological activity. Albumin is
the most common protein in blood, followed by the protective immune system proteins
known as immunoglobulins, which are involved in the recognition and adhesion processes
of cells. However, because exchange between absorbed proteins occurs, the final layer of
absorbed protein may be fibrinogen, which although less abundant, may have a greater
affinity for the biomaterial surface. The important message is that proteins guide cell attach-
ment, proliferation, and differentiation, so it is important to know which proteins are
attached to the biomaterial after implantation. The specific proteins that may have been
deliberately and carefully placed on the biomaterial before implantation, may no longer
be available to the cells after blood contact due to additional adsorption of blood proteins.
Blood coagulation is directed by attachment of the protein clotting factor XII, which is
found in blood, to the foreign biomaterial surface. After attachment of this factor, platelets
from the blood can and will adhere to the biomaterial, which leads to fibrin clot formation.
A cascading chain of cellular reactions that is governed by the initial protein attachment
begins. Blood contact provides the cells and cytokines that participate in the biological inter-
action with the biomaterial. Therefore, every biomaterial that contacts blood and absorbs pro-
tein will elicit biological responses from the body. In the case of artificial blood vessels,
formation of a blood clot must be avoided to prevent thrombosis, which is the blocking of
flow through a blood vessel by a blood clot. An effective and widely used method for pre-
venting surface-induced thrombosis of polymer materials intended for contact with blood
is by modifying their surface with heparin, through the ionic or covalent addition of this
anticoagulant.
