Tag Archives: medicine

Curing Cancer: a Giant Problem with a Nano- Solution

What if scientists could treat cancer without the extreme side effects of chemotherapy? Could scientists create a tiny way to cure a giant health crisis? Nanoparticle drug delivery systems could be the answer to our prayers.

Image of nanoparticles (small red circles) in a rat brain that has a tumor (green string-like material)
Nano-particles (red) in rat brain with tumor (green). Image taken from Washington Post.

Almost everyone knows a friend or family member who has had cancer and suffered through chemotherapy to recover. Currently, chemotherapy for treating cancer causes extreme side effects. For years, scientists have been researching methods to mitigate the adverse effects of treating cancers with the hope of one day creating a cure.

Delivering therapeutic drugs via nanoparticles (NP) are currently used in some FDA approved cancer treatments. Nanoparticles are extremely small–on the scale of the cells in our body. This is even smaller than a strand of hair on your head. Their size makes them ideal candidates for transporting drugs to tumors without damaging healthy tissue . In theory, NPs could hold drugs inside them, travel through our blood (ignoring healthy cells) and deposit the drugs right into the tumor.  However, there is a lot of research and improvements to be made before NPs can live up to their full potential. One of the largest unknowns in the study of NPs is their mechanical properties and how these properties interact with the body.

How does our body automatically know how to function without us telling it? Our body has biological sensors which govern our bodily functions in response to the world around us. For example, to prevent unwanted particles that may enter our bloodstream from getting to our brain or lungs, we have filters (like the spleen) that prevent them from passing through. Blood cells are soft, so they can squeeze through biological filters that dirt or stiffer blood cells could not pass through. To reach cancer cells, NPs must pass through these filters.

Stiffness is a mechanical property that measures how much an object moves when it is pushed on. Greater stiffness corresponds to larger applied forces.  For example, a piece of wood is stiff but a pillow is soft because it is easier to dent a pillow than to dent wood. To deliver NPs to the tumor through blood, the NPs have to get through the biological filters as they flow through the blood.

Image of blood cells squeezing through cell walls. Imagine a trying to push a pillow through a narrow opening. The blood cells (pillow) deform to pass through.
Blood cells squeeze through spleen walls, which acts as a filter for foreign objects in the bloodstream. Image taken from Zhang, et. al.

To allow passage through these filters, the NP’s mechanical properties must mimic blood. Scientists have performed tests on NPs with various stiffnesses and found that the soft NPs (like blood) were more likely to be allowed through the biological filters, whereas the stiffer (harder) NPs were blocked. If the NPs are blocked, they cannot travel through the blood streams to reach the tumor and are thus ineffective in treating the diseased cells.

The NPs (represented by the red circles) travel further into the tumor (blue and irregular shaped) than the stiff NPs do, allowing for more effective drug delivery. Image adapted from Hui, et. al.

Furthermore, soft NPs have been shown to penetrate deeper into tumor cells. The soft NPs can deform, allowing them to maneuver through the gaps between tumor cells (intercellular spaces). The deeper the NPs travel into the tumor, the more effective the drug treatment will be in attacking cancerous cells.

Nanoparticles hold the potential to revolutionize cancer treatment and prevention. By optimizing the mechanical properties of NPs, they could automatically release drugs in the presence of the tumors in response to their biological environment without delivering drugs to other cells. Further development of nanoparticle drug delivery methods may one day lead to a cure that will save loved ones’ lives. 

Why your scar tissue isn’t an issue

What do knee scrapes, adolescent acne, and paper cuts have in common? They all have the potential to leave a nasty scar. For people who have undergone trauma that results in serious wounds, especially on the face, scar aging is a serious concern. What are scars, and why does scar tissue tend to look different than regular skin as aging occurs?

In 1861, Karl Langer began observing the nature of the skin’s tensile properties. He cut small, circular holes into cadavers, and looked to see where on these holes the skin pulled the most. From these experiments, he developed “Langer’s Lines,” which he asserted were lines of tension all around the human skin. Later, Borges noticed that Langer’s lines only applied to cadavers, and began to perform similar experiments on live people to see if he saw different results. He pinched the skin of live people, and then saw how the direction of pinching impacted the length of the wrinkle formed. From these experiments, he identified RSTL, or relaxed skin tension lines. More and more researchers after Langer and Borges investigated the “tension line” phenomena, and they all noticed the same thing: wounds cut across these lines always led to nastier, uglier scars than wounds parallel to the tension lines. Why would that happen?

Figure 1 outlines the differences of Langer's lines, Kraissl's lines, and Borges's RSTL on the human face.
Image courtesy of MedMedia

To answer this question, let’s first identify the cellular mechanisms at work during healing. According to David Leffell of the Yale School of Medicine, there are three key stages of scar formation. The first stage of scar formation is inflammation. This happens right after the wound is incurred. Blood flows to the site, and tissue called granulation tissue begins to form at the base of the wound. Next is proliferation, when that granulation tissue helps the surrounding fibroblast cells to duplicate as quickly as possible. Fibroblasts are very important; they are the cells that produce collagen, a key protein in tissue formation. During proliferation, more and more fibroblasts fill the site, and they begin rebuilding the collagen networks for new skin. The final stage of scar formation is maturation/remodeling, when fibroblast levels decrease slowly as fresh tissue is rebuilt.

This figure shows each stage of wound healing, as is outlined by the supporting paragraph.
Image courtesy of biodermis.com

Because scars are formed differently than regular skin, they also tend to age differently. Normal consequences of skin aging can be seen around us in older people every day. As you may notice in your parents and grandparents, older skin tends to be dry, rough, wrinkly, and sometimes discolored. While these changes can also occur within scar tissue, the biggest factor in scar tissue aging is the difference in the rate of skin cell renewal. Skin cell renewal occurs when new skin cells travel from the basal layer of the skin up to the epidermis. Scar tissue’s renewal rate is different than normal skin’s renewal rate. This is why adults recover from wounds more slowly than young people – there is a greater difference between their cell renewal rates. The age at which the scar was formed, and the quality of the care provided, are critical in evaluating how well the scar will age.

If you’re interested in learning more about how that cut on your hand might heal and age, watch this video from TED-Ed, or for more detailed reading, check out this article.

Ways to Prevent and Treat a Common Annoyance: Headaches

Headaches can range from a mild annoyance to a debilitating condition that results in the inability to complete simple daily tasks. Odds are you have experienced a headache since about 50% of the population has suffered some type of headache. While there are many different variables that may have triggered it (injury, stress, chemical imbalances, etc.), the resulting symptoms are always negative. Scientists have been investigating what causes different types of headaches in hopes that they can help people prevent their occurrence and mitigate their symptoms.

One of the most common types of headaches is a cervicogenic headache – a secondary headache caused by referred pain from the neck to the head and facial regions. The high prevalence of cervicogenic headaches – 70% of people who suffer from headaches – prompted one study using a MyotonPRO device to measure and compare the tone, stiffness, and elasticity of the suboccipital and upper trapezius neck muscles in people who have and have not suffered from cervicogenic headaches.

Human suboccipital muscles located underneath the back edge of the skull.
Modified from BodyParts3D, Copyrightc 2008 Life Sciences Integrated Database Center licensed by CC Display-Inheritance 2.1 Japan.

Human trapezius muscle shown spanning the upper back through the neck.
Modified from BodyParts3D, Copyrightc 2008 Life Sciences Integrated Database Center licensed by CC Display-Inheritance 2.1 Japan.

The results showed that the tone – the degree of tension in a relaxed muscle – and stiffness – movement ability of the muscle – values were significantly higher in people who have suffered from cervicogenic headaches in the past. This can likely be attributed to overuse or high levels of past activity of these muscles. This can cause inflammation or other physiological changes that aggravate the nerve fibers in the neck resulting in a cervicogenic headache. The tone and stiffness data can be used to help educate patients on the importance of properly stretching their neck muscles before and after physical activity in order to keep them from tightening and shortening due to overuse. Muscle relaxing medications could also be used as a type of treatment when someone is suffering from a headache.

Tone and stiffness data for people with and without cervicogenic headaches.
Modified from Park, et al., The Journal of Physical Therapy Science 2017.

Another common type of headache is a migraine – a primary headache that has occurred multiple times throughout someone’s life. While a migraine can also have many different triggers, one study investigated the impact of a chemical imbalance of dopamine. This study found patients who suffer from migraines experience a decrease in dopamine levels before they feel the symptoms. There are a couple theories as to why decreased dopamine levels result in migraine symptoms: 1) decreased dopamine increases sensory sensitivity which may result in normally painless signals becoming painful, 2) decreased dopamine impacts motivation and reward/aversion to a point where patients withdraw and seclude themselves. In general, these findings can be useful for the advancement of dopamine regulating drugs in order to combat migraines. Further reading on different chemical causes of headaches in mice can be found here.

Figure showing dopamine levels decreasing during the onset of a migraine.
Modified from DaSilva, et al., Neurology 2017.

Overall, there are many different headache triggers and a lot more research needs to be done before science fully understands how they work. However, there are some things people can do now in an effort to lessen the probability they will suffer from headaches. Additionally, there are  medications and other techniques that work through different paths to mitigate the symptoms of a headache.

Can we 3D print our own skin?

Can you imagine a world where amputees receive replacement limbs which are able to detect temperature and pressure like an actual limb? How about a world where when you get a cut, you can 3D print some of your own skin to patch the wound?

To the average citizen, this might seem like something out of a science fiction movie. To researchers at the Graz University of Technology, the Wake Forest School of Medicine, and the Universidad Carlos III de Madrid, this is a reality that they are helping bring ever closer. Both of these scenarios are discussed in a recent article by Mark Crawford, who investigated the recent breakthroughs in 3D printing human skin and creating sense-sensitive artificial skin.

photograph of an arm reaching into the sky to feel the rain in the palm of their hand
photo by Alex Wong on Unsplash

At the Graz University of Technology, researchers are working on creating an artificial skin that can sense temperature, humidity, and pressure. Currently, artificial skins can measure one sense at best, but with the use of the nanoscale sensors that these researchers are developing, sensing all three at once could be possible. This is achieved through the materials that the nanosensors are created out of: a smart polymer core and a piezoelectric shell. The smart polymer core can detect humidity and temperature through expansion, and the piezoelectric shell detects pressure through an electric signal that is created when pressure is applied. With this technology, prosthetics could be made which could allow the wearer to retain some of their lost senses.

At the Wake Forest School of Medicine, researchers have created a handheld 3D printer which produces human skin. This device could be used to replace skin grafts, as it can apply layers of skin directly onto the wound. Through the use of bioink, this handheld printer can create different types of skin cells. After scanning the wound to see what layers of tissue have been disrupted, it can print the appropriate skin needed to correct the injury.

Photograph of the 3D skin printer created at the Universidad Carlos III de Madrid, which is still in its prototype phase.
modified from Crawford, ASME January 2019

At the Universidad Carlos III de Madrid, researchers are also 3D printing human skin using bioink. They are creating both allogenic and autologous skin to create the optimal skin, which is a combination of the patient’s own cells and cells created from a stock. Although they have managed to print functioning skin in its natural layered state, it is tricky to create the cells in such a way that they do not deteriorate.

It is also tricky to correctly deposit the product. To illustrate, more research needs to be done on the mechanical properties of artificial skin before it could be used on humans. The artificial skin must be able to stretch and react to tension in a similar manner to the real skin it will be connected to. Additionally, researchers must figure out how to safely send the signals the artificial skin is detecting to the brain.

Overall, both advancing artificial skins and 3D printing human skins could largely impact humanity. Even though we have yet to use these skins on people, they are already being used in industries, such as L’Oreal, to limit testing on humans and animals. Already, these skins are being used on robots, as seen in this video, to help prepare the skin for human transplant:

 

Interested in seeing more? Check out some more articles on the advancement of artificial skin from Caltech and Time.