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HYDROXYAPATITE - FROM DENTAL CARE TO CANCER TREATEMENT

  By Nicola Stanisławska & Maria Rutkowska

Do you ever wonder what is inside the toothpaste you use? Its contents are carefully selected to contain diverse types of ingredients that assist in the upkeep of your dental health. An example is fluoride - a naturally occurring mineral that keeps teeth strong, suppressing acid production and promoting remineralization in places where cavities are just beginning to form. But have you heard of hydroxyapatite? Although you won't find it in every toothpaste, it plays a role in helping to keep your teeth strong and healthy through its various properties. Moreover, these qualities allow for its use in different fields, such as bone repair, archaeology and even the treatment of bone cancer.  

 

Ever since it was first developed in the 1970s by NASA as a response to the loss of minerals in the teeth and bones of astronauts due to gravity, it has had a major impact on the field of healthcare, especially in the process of teeth regeneration. But you may wonder- what chemical properties allow for this to occur? 

Hydroxyapatite is a compound of calcium, phosphorous, oxygen and hydrogen with a chemical formula of:

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It crystalises in a hexagonal structure and makes up from 50%-70% of our bone structure. It can be grinded into micro and nano sized particles, with the nano sized particles proving to be especially useful in drug delivery. Moreover, it is typically extracted from natural sources, such as fishbone, coral, bovine bone, eggshell, and seashells.

When compared to other calcium phosphates, hydroxyapatite is more stable, which is an important property. Moreover, it is not excessively soluble, hence it does not react with our bodies negatively nor does it break down or disappear. 

 

This allows for it to be used in the medical field- under the pressure of physiological parameters such as body temperature or pH, hydroxyapatite is the most stable calcium phosphate molecule thermodynamically.

 

Furthermore, as hydroxyapatite makes up a substantial proportion of our bone and has the capability of supporting it in growth without degrading or dissolving, it is considered fully biocompatible.  

Now that we know the history, chemical composition, structure, and properties, what is hydroxyapatite currently used for?

As hydroxyapatite is the main structure in our teeth - it makes up 97% of the enamel and 70% of the dentil, it is considered highly biocompatible. It has been found to have a crucial influence on the health of our teeth through its use in toothpastes.

The dentil of our teeth is composed of dental tubules- small, hollow microscopic tubes travelling from the pulp to the dentil, ending right beneath the enamel. These are filled with a matrix of fluids pumped in and out of the pulp.

When a cavity is formed on the enamel, the dental tubules are no longer sealed, forming communication between the oral cavity and nerve. This can cause pain or sensitivity when touched. Moreover, the opening of these tubules can have a detrimental effect on the tooth as a whole- if enough bacteria enters these tubules and consequently becomes in contact with the nerve, it can become infected and even die.

As nano-hydroxyapatite is much smaller than the openings of these tubules, a high concentration can be used to seal these through filling the area. Consequently, the hydroxyapatite remineralises these tubules and the enamel, forming a bridge over them.

An advantage of hydroxyapatite over commonly used toothpaste ingredients, such as fluoride, is its autonomy. While fluoride requires saliva to activate itself as it mixes with phosphate and calcium ions in it to form a fluorapatite coating, as hydroxyapatite already contains these minerals, it does not require saliva to perform its function. Therefore, it does not depend on the concentration of saliva in a particular oral cavity.

Another revolutionary use of hydroxyapatite is the treatment of bone cancer. 

In 2022 alone, 3910 new cases of bone cancer have been diagnosed, one of the main types being osteosarcomas (Science Direct, March 2022). These are highly malignant solid tumours, typically affecting children and adolescents. Their current treatment protocol focuses on the use of Methotrexate, doxorubicin (Adriamycin), and cisplatin (MAP) with this drug regimen providing significant improvement for some patients. However, studies have shown that approximately 40% of osteosarcoma patients exhibit an unsatisfactory response to the current chemotherapy protocol, triggering the need for new treatment solutions. A study performed by researchers- “Bone mineral: A trojan horse for bone cancers. Efficient mitochondria targeted delivery and tumour eradication with nano hydroxyapatite containing doxorubicin” - proved that nano-hydroxyapatite can assist in apoptosis- cell death of osteosarcoma cells. Nano-hydroxyapatite particles can functionalize with doxorubicin and get engulfed in the lysosomes of osteosarcoma cells where the acidic microenvironment can cause the separation of the two particles. The released doxorubicin can then accumulate in the mitochondria, causing cell starvation and apoptosis - cell death.  

In conclusion, hydroxyapatite is an essential component of our skeletal system, making up to 90% of our teeth and 60% of our bones. Due to its outstanding properties such as biocompatibility, non-toxicity and osteoconductitiy, researchers and scientists have developed methods to implement this compound in dentistry, bone repair and regeneration. Moreover, with the rapid pace of new research and novel methods of scientific testing arising, hydroxyapatite has been found to assist in drug delivery, an example being the delivery of doxorubicin in the process of ostrosarcoma treatment. 

With these fantastic properties and it various already discovered implications, hydroxyapatite has a bright future with research that will bring us new technological advances. We must wait and see what the future holds.

So, the next time you brush your teeth and wonder what chemicals you are brushing onto your teeth – you will know. It is hydroxyapatite! 

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