|A Message from the Executive Director:|
This is a missionary Center, bringing the message that many seemingly diverse fields are but a single field when attention is focussed sharply enough at the various phase boundaries. A common feature often found is that the boundary interactions are dominated by interfacial layers of biological origin. Thus, advances in applications of materials at biological interfaces will be achieved more rapidly if individual gains from previously isolated disciplines, all of which involve biological interfacial phenomena, can be integrated. For example, this Center demonstrates that most fields of biological adhesion are unified at the fundamental level where one must deal with attachment of single cells or small multicellular aggregates under moist, saline, and biochemically active conditions. The events of maritime fouling, thrombus formation, and dental plaque attachment share marked similarities in the established requirement that all solid surfaces first acquire a conditioning layer of protein which mediates the adhesive interactions with arriving cells. At the electron microscopic level, specimens from biological milieux of sea water, blood, or saliva or tears can seldom be differentiated. Apparently insurmountable difficulties in some fields have already been overcome in other phases of biological surface science.
This Center grew from a perceived need for cross fertilization of these artificially separated disciplines.
Here are some excerpts from our introductory article (CHEMTECH, MARCH 1986, pages 178-185), "Biosurface Chemistry for Fun and Profit" (R.E. Baier and A.E. Meyer)
"Imagine yourself cruising in a sleek, new fishing boat off the Atlantic shore, making good speed, when suddenly porpoises, so common in these waters, begin to frolic near your boat. Although you are going as fast as you can, these friendly marine mammals probably will not only keep up with you, but will swim circles around you, even without riding your bow wave.
After some six months in the water you will find that your vessel will not be able to make anywhere near the top speed it did when it was freshly launched with a new coat of antifouling paint. However, the porpoises and their cousins, the killer whales, who will have been in the water much longer than your boat, will have no trouble maintaining their speed.
The questions a biosurface scientist asks about this are "What has nature wrought with regard to the interfacial layers of these once-terrestrial creatures?" "Can we mimic it to provide truly nontoxic, fouling-resistant, low-drag coatings for our vessels, or perhaps even for pipelines taking in cooling water for coastal power plants?" "What can we learn from surfaces within the human body, such as eyeballs and teeth and blood vessels?" In the past two decades, many new and exciting techniques have allowed a much closer look at the actual boundary phenomena where biological systems meet synthetic materials."
To find out how Mother Nature does it, we have studied the surfaces of porpoises and killer whales as our "research partners" at various research aquariums, using the same analytical methods on the living surface layers of these mammals as we first applied to our own skin, teeth, and even to human blood vessels. The simplest and most rapid of these techniques is not new: In 1805 Thomas Young applied test droplets of fluids of known surface tension and measured their contact angles to estimate their wetting and spreading tendencies. Using internal reflection IR spectroscopy on full-thickness skin layers from porpoises and killer whales, we learned that, similar to human skin, they contain proteins, carbohydrate-modified proteins, and a lot of lipid (fatty) materials. Using transmission electron microscopy, we found that the actual outermost aspect of the living porpoise and killer whale skin is dominated by a thin, amorphous layer that consists of a quite pure glycoproteinaceous material. We learned an interesting lesson from oil droplets (probably from half-eaten fish) that occasionally cling to the surface of the tissue. These droplets exhibit a finite, nonspreading contact angle on the surface.
In the Old Testament, Job says, "My bones cleave to my skin and to my flesh, and I escape death by the skin of my teeth" In fact, we have discovered the causes of the differences in "skin" surface properties of materials in the human oral cavity. They result from the differential qualities of the spontaneously acquired "pellicles," usually very similar glycoproteinaceous subfractions from the salivary pool that rapidly adsorb and differentially orient at the salivary boundaries with different dental materials. The mucosa in the mouths of land-dwelling mammals, such as humans, monkeys, and dogs, has a nearly identical architecture to the external skin layers of porpoises and killer whales. (It is important to note that all techniques described here are approved by research committees at the participating research institutions and also carefully evaluated for conformance to requirements of the Marine Mammals Protection Act.)
It was especially revealing that standard polishing procedures for dental implants led to interfacial scarring, poor adhesion, and weak abutting tissue, whereas scrupulously clean, high-energy metals of the identical bulk composition result in minimal interfacial scar tissue, dramatically increased cell activity, and bioadhesive strength equal to the greatest strength possible in that biological system, the cohesive strength of the tissue itself. In bone, this is called "osseointegration".
Application of physical and chemical techniques
Seven nondestructive interfacial analytical techniques are routinely applied in sequence to the same thin biological deposits still in place on the test materials under investigation. We use IR spectroscopy to determine chemical composition, ellipsometry to determine film thickness, contact angle measurements to determine the surface tension (a most useful bioengineering characteristic), and scanning electron microscopy (SEM) to characterize the surface texture and the morphology of such specimens. Later, we add x-ray diffraction and photoelectron spectroscopy for finer details.
Most of the same techniques can also be applied to interesting biological tissues themselves. We have already mentioned some of the results from the analysis of porpoise and killer whale skin; Nature's most nearly perfect fouling resistant surface is the intact, closely packed, endothelial lining inside a blood vessel. Just beneath the pavement of endothelial cells is, unfortunately, one of the most fouling-prone materials ever characterized - the subendothelial lining or basement membrane. This layer has evolved properties that cause immediate platelet adhesion (a kind of biological "hot patch" technique) to cause clotting and prevent us from bleeding to death.
Imagine the thrill when we and our colleagues were able to fully remove this endothelial lining and restore the subendothelial lining, by manipulation of its surface chemical qualities, to a functionally thromboresistant surface. These substitute blood vessels were fully approved as peripheral vascular grafts for human implantation by the Food and Drug Administration in 1979 and are now "walking around" inside more than 80,000 people worldwide, who have been saved from amputation or perhaps even death resulting from the ravages of atherosclerosis.
As most artificial organ enthusiasts know, there also was some success with completely synthetic chambers for handling human blood, such as the pumping bladder inside the Jarvik artificial heart. We had the privilege to be associated with the pioneering effort for the production of functional, total artificial hearts and left ventricular assist devices, led by William Pierce at the Hershey Medical Center.
It was not a trivial procedure to produce this successful material from a basic polymer (polyurethane) sold predominantly for construction of women's undergarments and running suits.
Like the sharp boundary between light and shadow, thrombus and coagulum formation on synthetic materials surfaces can be observed to change from complete fouling to no fouling within the distance of a few red cell diameters. This bodes well for the construction of increasingly useful biomedical devices, such as improved synthetic heart valves, in which we need tenacious biological adhesion around the sewing ring that holds the device in place next to the struts and valve poppet, where no adhesion is wanted.
Another surprise, although this one has
gone more than two decades without commercial exploitation, is that we
can prevent glass surfaces from causing clotting. All medical texts
agree that glass is the best clotting surface. But when properly
treated (for example, by the glow discharge process in argon followed by
storage in boiled distilled water to keep the surface clean and of high
energy while encouraging formation of glassy hydrogel), we can prevent
local induction of blood clotting and thrombus formation. This may
be more a curiosity than a useful fact at the moment, although we do envision
applications for similarly treated metals, metal oxides, and ceramics in
the near future.
Another surprise is that surface trenches not exceeding 1 micrometers in either breadth or depth are easily tolerated by flowing blood. The peaks and valleys are quickly leveled by the deposition of plasma proteins without significant ill effects on the remainder of the flowing blood system. This observation will permit less extreme surface polishing of useful biomedical materials. Significantly, high-surface-energy, mirror-smooth metal specimens induce tenacious adhesion of biological debris.
On a grander scale, we have succeeded in producing automatic devices for the U.S. Navy that glow discharge treat and clean periscope windows. Then, the devices coat the windows with minimum-surface-energy coatings that allow our strategic submarines to fulfill their missions without the periscope windows becoming obscured by oceanic fouling films.
Don't poison the patient, or the environment
The big payoff has come in the production of truly nontoxic fouling-resistant marine paints to replace the poisonous resins used around the world. As biomedical engineers and biosurface chemists, we shouldn't poison our patients under the guise of keeping their plumbing clean. There are, indeed, surface chemical and physical principles that work, as the long-term experience (now in excess of 20 years) with some 80,000 human cases for the umbilical vein graft has shown. We must consider the same options for the external environment. Indeed, we are engaged in such a venture, and our most significant successes have been with formulations similar in almost all respects to those that we used in the artificial heart. Nature is very conservative, accepting as its minimum adhesive surface the same cluster of closely packed methyl groups for blood and seawater systems alike.
We are enthusiastic about the progress
yet to be made and welcome the many new practitioners of this old but exciting
science to our Center!