One Size Does Not Fit All: The Journey to Biocompatibility
by Gary M. Verigin, DDS, CTN
When you have a decay-riddled or broken tooth, it’s not too tough to get it fixed. You go to your dentist, and your dentist fills it or replaces it with a prosthetic appliance. This repair work is part of a specialty called restorative dentistry. In performing it, dentists have such a wide array of high-tech tools and materials at their disposal, it seems it must be a relatively modern invention. But as a matter of fact, restorative dentistry is nothing new.
A Brief History of Restorative Dentistry
More than 6000 years ago, the Chinese and Sumerians used foreign materials to fill decayed teeth and treated the oral tissues with medicaments. They also knew that oral hygiene and the prevention of dental disease were somehow related. Three thousand years later, “tooth doctors” were recognized in Egypt as medical specialists. By 700 BCE, the Etruscans were replacing missing teeth with prosthetic appliances, fastening human or animal substitutes onto existing teeth with gold bands and wires.
About 200 years later, the Estrucans were conquered by the Romans, who habitually adopted the most useful knowledge and technologies of each culture they overtook. Some of the imported Etruscan dental practices became quite popular. For instance, the poet Martial tells us that it was common and somewhat fashionable to wear false teeth. From the writings of Celsus, we also know that by 100 CE, lead was the filling material of choice for decayed teeth. Broken teeth were often filled before extraction, too, as the metal made teeth less apt to fracture during surgery. Fifty years later, Galen became the first to describe the importance of removing decay prior to filling. He was also the first to describe dental nerves.
We don’t know exactly how long the lead treatment remained common, but by the Renaissance, other materials had come into use. In 1480, Arculanus, a Bolognese professor of medicine, wrote of filling decayed teeth with gold foil. In the early 16th century, Paracelsus wrote of the effects of different metals on the body.
The late 17th century marked a renewed interest in scholarship – one that grew exponentially throughout the Neoclassical Age. The interest spanned all areas of knowledge, including dentistry. The first major English language work on the subject appeared in 1685. In France, Fauchard published his work on dental surgery, Le Chirugien Dentiste, in 1728. Back in England, nearly 50 years later, Hunter published The Natural History of Human Teeth. This work established dentistry as a distinct branch of Western medicine.
As the Industrial Revolution progressed, the idea of dentistry as a craft came to the fore. New technologies quickly arose. In 1790, Greenwood – the American dentist who made George Washington’s false teeth – developed a foot-powered drill. He also explained the importance of cavity preparation design in the effective use of dental filling materials. These early 19th century fillings consisted mostly of tin and lead. Fox later developed a version that added bismuth.
Meanwhile, the Chinese had introduced mercury and silver fillings to the French. As filling material, it had two main virtues: it was cheap and could be inserted quickly and easily. Working from Fox’s model, Bell developed a mercury amalgam filling in 1819. Taveau followed with another in 1826. By mid-century, the use of mercury amalgam fillings was wide-spread.
Many bitter disputes arose over the biocompatibility of mercury amalgam. In turn, clinical and scientific researchers explored its effects on the human body. As early as 1861, in England, Tomes was performing experiments on amalgam shrinkage. From about 1871 to 1874, Fletcher measured marginal leakage through the use of dyes. Meanwhile, in the US, Hitchcock used micrometer devices to measure amalgam dimensional charge. Others were inspired to develop new techniques and what were thought to be improved materials. Most concepts and many materials used in dentistry today resulted from these and other 19th century studies.
By 1895, Black’s famous and brilliant research on dental materials was well underway. Looking into the physical properties and clinical performance of mercury amalgam, he was convinced that it should never be placed in the same mouth as gold. Black also recognized galvanic current and advocated scientific cavity preparation to keep decay from recurring at a restoration’s margins. Today, historians acknowledge him as a pioneer in the science of dental materials. His textbook Operative Dentistry continues to influence dental practice.
While Black was investigating dental materials, Ames and Fleck conducted their early research on dental cements. This work led to the development of modern phosphate cements. About this same time, Philbrooke developed the lost wax process of gold casings. This process was publicized and patented by Taggart in 1907.
Despite these innovations, few appreciated the biological effects of dental materials on human tissue and individual biochemistry. The traumatic effects of dental surgery weren’t even understood. Some dentists pounded away at the pulp when inserting gold foil restorations. Some used the poisonous heavy metal arsenic and strong acids to cement their gold work. Some applied creosote to freshly cut dentin and exposed pulps. Not surprisingly, their patients usually experienced terrible pain. Most – patients and dentists alike – believed this was just a consequence of clinical dentistry. Few suspected it had anything to do with the choice of materials and medicaments. Even fewer thought about their long-term effects.
During this era of mechanical dentistry, most dentists – and the public – had only the most basic functional concerns about what was being placed in people’s mouths. These included issues of durability, physical performance and the maintenance of mechanical function. This philosophy of dental materials held sway until quite recently. Yet as early as the mid-1930s, Skinner was urging dentists to consider the importance of the biological aspects of cements.
Concern with the possible toxic effects of dental materials grew after World War II. At first, researchers seemed preoccupied only with effects on the dental pulp, but as more synthetic materials were developed for dental use, the focus shifted to biomaterials. With so many synthetics coming into use, there was a much greater need to test them before placing them in anyone’s mouth. As Smith and William stated in their 1982 epic Biocompatibility of Dental Materials, “It is irrational to insert a synthetic substitute for a bodily tissue without first ascertaining the properties of the natural tissue as well as those of the substitute.”
Evaluating the Biocompatibility of Dental Materials
In determining biocompatibility, several variables must be considered. For instance, visible reactions to exposure may differ among individuals. When symptoms aren’t visible, when they are evident only to the person experiencing them, serious conflict may result between practitioner and client. The duration between exposure and symptom onset must be taken into account. One must also consider the range and type of environmental toxins, heavy metal accumulations or allopathic medications the individual is subject to. Any one of these can contribute to unexpected reactions.
Dental materials may be aesthetic and durable yet leech various combinations of the organic and inorganic byproducts of corrosion and degradation. This can cause problems for those with systemic sensitivities. As Jess Clifford notes, “In the breakdown sequence, some tissues can be adversely affected and their function impaired. Still other tissues may not tolerate the presence of abnormal galvanically generated electrical interference or adverse effects of electrically and chemically stimulated aberrant metabolites on cellular DNA and mitochondrial sites when the restorative material byproducts become involved in various metabolic activities and pathways.” In short, the byproducts can act as poison and hijack one’s immune system.
Several factors influence the distribution, metabolism and toxicology of synthetic dental compounds and alloys. The presence of other metals, metalloids and synthetics can alter the dose-effect and dose-response relationship of elements. This has definite practical consequences. For instance, the sequence of exposure helps determine whether the foreign materials will be taken synergetically or antagonistically. Will the body accept them or fight them? Sometimes, the client may grow more sensitive to one compound and less to another. Exposure to multiple compounds can affect the client’s safety margin more than exposure to a single alloy or compound.
The sensitive client may already carry a great many chemical and physical burdens from non-dental sources. The treating dentist should not add to this person’s burden. Here, it is especially important to remember that the materials placed in the teeth stay with the person 24 hours a day, 365 days a year,for decades. In light of this constant exposure, evaluating the materials to be used becomes even more important. The client’s health depends on it.
The practicing dentist must be fully aware of the long-term systemic effects of treatment. Dental procedures and materials can affect almost every organ, tissue and molecule of the body. In the end, it’s more important to consider the quality of the client’s total systemic health than issues of durability and aesthetics. According to David Williams of the University of Liverpool,
The meaning of the term “biocompatible” as it is applied to dental materials…has a broader spectrum than for many other surgical materials and requires a wider interpretation as a basis for a decision as to safety and efficacy – a decision which is incumbent on the manufacturer and on the clinician. In the present state of knowledge no absolute decisions are possible: hence, clinical use of materialsis only permissible on the basis of informed judgments.
This was Williams’ opinion in 1982. At that time, testing focused on components and analyzed factors such as physical and tumorigenic effects, galvanic phenomena and radiation. Microbiological factors were also considered. Researchers placed the materials in contact with mucous membranes and other soft oral tissues, and noted their effect on the dental pulp and adjacent tissues. They also evaluated the composition of root canal filling materials and tested their effects on the health of the dentin and tooth enamel.
The chemicals, alloys and synthetic compounds used in dentistry can cause an array of reactions and sensitivities: allergic, toxic, pharmacologic and immunologic. Though these might not overlap completely, most tend to involve immune reactivity.
Immune reactivity from dental materials has been tested using the scientific gold standard: the double-blind test method. Four methodological factors were considered: dual Ouchterlony diffusion, precipitin reaction, red blood cell hemagglutination and cell surface phenomena. Researchers concluded that dental materials can indeed produce immune reactivity in humans. They also advised that because materials testing had such merit, it should always be conducted prior to placement.
How does immune reactivity occur? Corrosion and degradation byproducts combine with protein molecules, forming haptenes and organo-metallic compounds. These are foundational to an allergic response. The immune system recognizes them as antigens: substances that provoke an allergic response. Seeing these substances as “non-selves” – foreign invaders, as it were – the immune system sets up several processes to remove them. For example, polymorphonuclear leukocytes (PMN) try to eliminate the challenge by a process called phagocytosis. The PMN engulfs the antigenic complex and tries to destroy it by secreting powerful enzymes called peroxidases to digest the foreign substance. If successful, the substance is excreted via the intestines, kidneys or lymphatic system.
Unfortunately, heavy metals can’t be broken down for disposal. Instead, the PMN itself may be broken down and haptenes, dumped into the bloodstream. The immune system then reacts to these products as antigens. This event can trigger far more aggressive immune reactions. Macrophages appear, which can readily generate pinocytosis: the uptake of fluids or other substances into the cells. In this way, toxic compounds are processed for elimination. T-4 helper lymphocytes secrete lymphokines, which in turn create B-lymphocytes. These B-cells and later-developed plasma cells then create antibodies called immunoglobulins, which are directed to the toxin or antigen.
Dental material reactivity testing is based on systemic challenges to the immune system, i.e., the creation of antibodies. Minimal responses such as a hypersensitive or allergic reaction will spur the creation of the antibody IgE. A skin rash is one such response. An initial reaction, however, usual generates IgM. About 10% of all present antibodies will be of this type. If byproducts are constantly released from implanted materials, the more specific IgG will form. These could comprise about 75% of the antibodies. The third type of antibody included in reactivity tests is IgA.
As soon as byproducts enter the body, the immune system also goes to work creating memory cells. These can live in the immune system for several years. When re-exposed to the toxins or antigens, these memory cells can launch an immediate IgG attack. Dental byproducts usually elicit IgM, IgG and IgA antibodies. The allergy antibody IgE may not even be stimulated. This is why skin-patching specific materials is no longer preferred: because the process doesn’t produce IgE, it can’t detect the full range of possible reactions.
In the worst case scenario, antibodies combine with the dental material byproducts to create antigenic immune complexes in the client. These complexes can lead to the self-attacking autoimmune diseases: failing to recognize itself, the immune system assaults itself.
When a toxic substance enters the body, it is considered a threshold event. Because toxins may be sequestered in different organs and tissues, symptoms may vary widely from person to person. Although toxins can be voided, they also can leave the person sensitized. An analytical follow-up measurement of the offending substance is often difficult, perhaps meaningless and often impossible. It simply cannot show the lingering effects of exposure.
Because of this, the systemic immune response – reactivity – is a much more reliable marker that the client has encountered substances that provoke an immune response. The effect of the exposure – perhaps not felt by the client clinically or even manifested immediately – may be deduced by the presence of antibodies. The simple presence of an antigen sets off an immune reaction. Even after the offending materials are removed or voided, or even sequestered in a tissue, the antibodies and memory cells remain.
Source Determination and Reaction
If a specimen is reactive to a substance in a particular dental material, it does not absolutely identify it as the contributing source. Accumulations in one’s tissues may be from previous environmental exposure. Restorative materials already in place also may be a factor. The reaction strength of the antibodies may be due to the currency, quality and quantity of exposure, the possible onset of tolerance and immune function strength. Because of this, degrees of reactivity all should be considered the same.
Accessory Methods to Evaluate Dental Material Suitability
- Electrodermal response
- Muscle testing
- “O” ring
- Skin/patch tests
Chestnut, R.W. and H.N. Grey. 1985. Antigen presenting cells and mechanisms of antigen presentation. CRC Critical Reviews in Immunology 5: 263+.
Clifford, J. 1990. Materials reactivity testing: Background, basis and procedures for the immunological evaluation of systemic sensitization to components which emanate from biomaterials. Working paper.
Huggins, H. 1989. Serum compatibility: A revolutionary approach to selecting safe dental fillings. Working paper.
Jaret, P. 1986. The wars within. National Geographic June 1986: 702-735.
Skinner, E.W. 1936. The science of dental materials. 1st ed. Philadelphia: Saunders, 1936.
Williams, D., and D. Smith. 1982. Biocompatibility of dental materials. 4 vols. Boca Raton: CRC P, 1982.