The mechanical devices implanted into biological systems are important;
they have increased the length and quality of life and promise to provide
even greater benefits in the near future. Equally as important are
the materials from which they are made, as well as the materials that “glue” them
into place. These “biomaterials” include living tissue
as well as synthetic substances.
As they continue to pursue minimally invasive procedures and other avenues
of research, Notre Dame engineers, biologists, and chemists are working
together to improve existing materials and create new ones that will
last longer, be more wear resistant, and even strengthen bone.
Understanding materials and how to engineer their properties on the molecular
level is vital. Why? “You can’t solve this problem if you
don‘t understand the molecules,” says Edward
J. Maginn, associate
professor of chemical engineering, of the cartilage wear project he is
working on with Timothy C. Ovaert, professor of aerospace and mechanical
engineering, and Schmid. “The phenomenon -- that the proteins naturally
present in synovial fluid lubricate cartilage joints much better than
polyethylene joints -- is due to molecular-level processes. Using molecular
modeling, we can simulate proteins in the synovial fluid at the atomistic
level as they interact with both natural cartilage and synthetic material
to understand how they lubricate surface areas. With this information
we can then work together on the macroscopic problem, engineering better,
more wear-resistant materials.”
Biomaterials, natural or synthetic, must also be in tune with the body’s
many systems. As strong as the body can be, it is delicately balanced.
Not every metal or composite is appropriate for use as a biomaterial.
For example, while steel and aluminum are common engineering materials,
they should not be implanted into biological matter. Tantalum is the
most biocompatible metal known. High-density polyethylene is also highly
biocompatible; it is basically the same polymer used in milk jugs. And,
polyurethane has been used extensively in artificial heart valves.
According to Ovaert, polymers are ideal for biomedical applications because
there is a low level of toxicity with the body. “The human body
accepts polymeric materials much more readily than a lot of metals or
other types of inorganic materials,” he says, “and they’re
inexpensive to process. Plastics (polymers) also offer greater wear-resistance
features in some applications.”
Mason, Schmid, and Davide A. Hill, associate professor of chemical engineering,
are working to develop new polymers for use in hip replacement and spinal
fixation applications. “The requirements for strength, fluidity,
and viscosity for the material in the hip application are completely
different from a spinal fixation project,” says Mason. “For
the hip application, we are working to modify bone cement.” Traditional
cements are currently used in thin layers between an implant and biological
tissue, but new applications -- like the minimally invasive procedures
the Notre Dame group is developing -- stretch the limits of the cements’ properties.
One of the main issues under consideration is thermal necrosis, the term
for the damage caused by the heat generated when a polymer cures in the
body. If the temperature is too high, the tissue surrounding the cement
is destroyed. “Bone cement heats when it hardens, and we’ve
been working to modify that, bringing the temperature down to more acceptable
levels,” says Hill. “We’ve also been studying photocurable
polymers, materials similar to what a dentist puts into a cavity to seal
it. We know that photocurable polymers heat very little when they cure,
which means less damage to surrounding tissue. What we are exploring
is whether or not we can design a new material, a biocompatible photocurable
Creating new materials is also the thrust of Ryan
K. Roeder’s research.
Roeder, an assistant professor of aerospace and mechanical engineering,
is working to design biomaterials that more closely match the mechanical
properties of human bone. “Bone is, in my opinion, the most original
and most incredible composite material around,” says Roeder. “While
there’s a great deal of excitement surrounding tissue engineering
today, we still don’t have a synthetic material that mechanically
functions identically to bone.”
Most of the materials currently used to replace or strengthen bone are
an order of magnitude stiffer than bone. What often happens, according
to Roeder, is that the stiffer material carries the load instead of the
bone carrying the load. It’s called stress shielding, and when
it occurs, the bone -- signaled by a decreased load and, hence, a decreased
need to be strong -- starts to resorb and pull away from the implant.
An additional parameter of Roeder’s ideal bone substitute is that
it should be able to serve as a vehicle for delivering growth factors
or cells to help bone repair and strengthen itself.
Given the nature of bone, this is a tall order. Bone consists of several
hierarchical structural features, which at the simplest level are comprised
of a biopolymer, namely collagen. The collagen is reinforced with elongated
ceramic particles or bone mineral. The particles are calcium phosphates
with a complex composition and crystal structure, which is most closely
resembled by hydroxyapatite, the material Roeder grows in aqueous solutions
in his lab and expects to use as a biomimetic reinforcement phase in
new synthetic biocomposites.
Roeder anticipates that, as the field of biomaterials develops, there
will be a shift from using relatively few materials for many different
devices and applications to designing devices using a variety of unique
materials, whose properties -- mechanical, biological, or functional
-- have been tailored for a specific application.
On any given day an average of 34,000 units of red blood cells are
needed ... for trauma victims, heart surgeries, organ transplants,
and patients receiving treatment for diseases such as leukemia,
sickle cell anemia, and thalassemia. Each unit of whole blood is
normally separated into several components. Red blood cells, which
carry oxygen and are used to treat anemia, can be stored under
refrigeration at 4 degrees Celsius for approximately 40 days. They
may also be frozen for up to 10 years. Platelets, vital in controlling
bleeding and often used in patients with leukemia and other forms
of cancer, can be stored at room temperature for up to five days.
Fresh frozen plasma, also used to control bleeding, is usually
kept in a frozen state and is viable for up to one year. Containing
a few specific clotting factors, cryoprecipitated AHF is made from
fresh frozen plasma and can be frozen for up to a year. Granulocytes,
sometimes used to fight infections, must be transfused within 24
hours of donation.
Donated blood is free, but there are significant costs associated
with the collection, testing, preparation, labeling, shipping, and
storage of blood. There are also costs stemming from the recruitment
and education of donors and the commitment to keeping the blood supply
free from contamination. Even if these costs were minimal, the blood
supply level is constantly fluctuating while the number of places
around the world that need blood is constantly increasing.
Blood may be transfused as whole blood or one of its components.
Because patients seldom require all the parts of whole blood, often
only the portion needed by the patient is transfused. This type of
treatment is called blood component therapy. However, almost all
of the components have a limited shelf life, and most require some
sort of refrigeration. In addition to these factors, blood types
must also be considered when planning a transfusion.
Andre F. Palmer, assistant professor of chemical engineering, is
working to create a universal blood substitute that will last for
years without refrigeration. He is also developing a novel vehicle
for delivering anti-cancer drugs.
“In our lab we make polymerized hemoglobin blood substitutes,” says
Palmer. “The unique aspect of this work is that we’re
developing new cross-linking agents to polymerize the hemoglobin.” By
creating large polymers of hemoglobin, Palmer will be able to control
the amount of hemoglobin that travels through capillary walls into
smooth muscle cells, where it normally sequesters nitrous oxide,
causing blood vessels to constrict and leading to high blood pressure.
Funded by the National Science Foundation and the National Institute
of Science and Technology, Palmer is also developing bubble-like
drug-delivery “vehicles” which can be injected intravenously.
Using sophisticated emulsion techniques, Palmer is creating a mechanically
strengthened “bubble,” similar to the polymerized hemoglobin,
that can withstand the forces of the blood flow in the human circulatory
system while targeting cancerous cells.
Palmer coats the surface of the vesicle with ligands that recognize
specific receptors on a cancer cell. So, when the ligand covered
bubble comes in contact with the cancer cell, the cell engulfs the
vesicle, digesting its contents, which is where the cancer-fighting
drug is stored. The cancer cell then dies from the inside out. Palmer
hopes to create a bubble that will remain in tact within the circulatory