Biomedical Engineering Reference
In-Depth Information
Both the occluder and the containment system are in direct contact with blood. Contact
with foreign materials can cause blood to clot and can lead to platelet attachment and clot-
ting. If the design results in eddy flow or stagnation, the clotting factors can accumulate and
lead to thrombus formation. Therefore, both the material selection and device design must
consider problems of blood contact and blood flow. Since these problems have not been
solved, patients with mechanical heart valves receive medication to reduce their tendency
to form blood clots.
Biological heart valves resist thromboembolism much better than synthetic materials do,
but they are less durable. The valves are harvested from 7- to 12-month-old pigs and pre-
served with gluteraldehyde fixation. The gluteraldehyde fixation slowly leads to unwanted
calcification of the biological valves and eventual failure. Tissue engineering approaches are
now being developed to synthesize living heart valves, but durability remains a large con-
cern. The muscle of the heart has not yet withstood grafting; however, stem cell technology
might be able to rebuild the damaged tissue in situ. Recent results from experiments in
which mesenchymal stem cells have been injected directly into the ventricle wall have shown
that a small fraction of the cells incorporate in the heart muscle and initiate regeneration of
damaged heart muscle. Whole pig hearts have now been decellularized and reseeded with
human cells to form a living, beating heart. Who knows what these breakthroughs will do
to the life expectancy of future generations?
5.7.3 Drug Delivery
Biomaterials play an important role as delivery vehicles for pharmaceuticals and bio-
molecules. The pharmaceutical industry has long used powdered biomaterials such as talc
and calcium carbonate to form pills and tablets containing a drug. The goal of drug delivery
research is to prepare formulations that will result in sustained active drug levels in the
body, leading to improved drug efficacy. Controlled-release formulations accomplish this
by various techniques that involve conjugation of the drug to a biomaterial. For example,
by delivering basic fibroblast growth factor bound to heparin, the blood circulation time
(as measured by a half-life) is increased by a factor of three. Conjugation to polyethylene
glycol (PEG) is a well-established approach for in vivo protein stabilization.
Nanoparticle drug delivery is a rapidly expanding field. Nanoparticles can be made of
metals, ceramics, and polymers. One example of a nanoparticle is a liposome. Liposomes
are made from phospholipids that form hydrophobic and hydrophilic compartments within
an aqueous environment. A unilamellar liposome has spherical lipid bilayers that surround
an aqueous core. Water-soluble drugs can be entrapped in the core, and lipid-soluble drugs
can be dissolved in the bilayer. Liposomal drug formulations exhibit extended circulating
half-lives after intravenous injection. The drug concentration in plasma over time is ele-
vated three to ten times when incorporated in liposomes.
Polymers are widely used in drug delivery systems. Nondegradable hydrophobic poly-
mers (silicone elastomers) have been used most extensively as semipermeable membranes
around drug reservoirs. Alternative formulations involve mixtures of drug and resorbable
polymer that release drug when the polymer degrades (Figure 5.18). Increasing the loading
of the protein or drug within the matrix increases the release rate of the compound. As a
rule of thumb, as the average molecular weight of the polymer in the matrix increases,
