Biomedical Engineering Reference
In-Depth Information
Basically, our immune system protects us through a combination of physical barriers, such
as skin, chemical barriers, such as enzymes and antibodies, and cellular barriers, such as
targeted cytotoxic T lymphocytes (T cells). When a biomaterial is implanted in the body,
the immune system-associated proteins found in blood immediately attach to the surface,
thereby directing the subsequent cell behavior toward the biomaterial. Once again, it must
be emphasized that the surface chemistry and structure of the biomaterial play important
roles in determining the extent and type of protein attachment and thus the tissue-
biomaterial interaction. Proteins of all types will be competing for attachment sites on the
biomaterial surface. Depending on the conformation of the attached proteins, a variety of
messages may be sent to the nearby cells. Methods for modifying the biomaterial surface
to control tissue-biomaterial interactions are discussed later in this chapter.
When allogenic (human) graft biomaterials are implanted in another human, acute rejec-
tion can occur if the major histocompatibility complex (MHC) proteins on the cells in the
graft are of different types than the donor's MHCs. MHCs are a class of cell-surface mole-
cules that provide information as to what has been identified as foreign in the past to the
cytotoxic T cells. With nonmatching MHC groups, the T cells receive two sets of instruc-
tions as to what is foreign, and this causes an extremely vigorous immune response. Tissue
typing can reduce this type of rejection, although the patient usually still requires long-term
medication to suppress some of the activity of the immune system. Rejection can also occur
against cell-biomaterial scaffolds in tissue engineering applications. The implanted cells
may be recognized as foreign and be damaged directly by the attacking immune cells such
as macrophages or be starved to death by the lack of nutrients passing through a thick
fibrous capsule created through the inflammatory process to protect the host. Therefore,
in some tissue engineering applications, the implanted cells are protected from the immune
system by enclosing the cells in selectively permeable biomaterials (e.g., islet cells that pro-
duce insulin in alginate hydrogels).
Corrosion of metallic implants releases metal ions that can cause metal sensitivity or
allergic reactions in some individuals. Allergic reactions can lead to slow or inadequate
bone fusion or skin dermatitis. Both of these conditions usually require removal of the
implant. Once again, this demonstrates that biomaterials are not inert.
Biomaterials are sometimes deliberately designed to enhance the immune system's res-
ponse. For example, vaccines are typically given with a particulate biomaterial known as
an adjuvant for enhanced and longer-lasting immunity. Vaccine adjuvants have their own
immunogenic properties, resulting in a stronger local stimulus to the immune system. Bio-
material adjuvants can be simple particles that adsorb the weak immunogen, increasing
the effective size of the weak immunogen and enhancing phagocytosis of the particle by
macrophages. Biomaterial adjuvants also work like controlled-release vehicles by prolong-
ing the local retention of a weak immunogen and increasing the chance of a local immune
response. Vaccine adjuvant selection represents a compromise between a requirement for
adjuvanicity and an acceptable low level of side effects. The FDA has approved only three
materials for human use (all of which are mineral salts): aluminum phosphate, aluminum
hydroxide, and calcium phosphate. Aluminum compounds are often incorrectly identified
in the scientific literature as alum. Alum is potassium aluminum sulfate that is used as the
starting solution to precipitate antigens with either aluminum phosphate or aluminum
hydroxide. Other biomaterial adjuvants used in research include oil emulsions, lipopolysac-
charide products from bacteria (LPS), and their synthetic derivatives (liposomes).
