Supramolecular Bonds and Thermodynamics

Last week's post on supramolecular bonds facilitates itself for a new post about a topic that is taught in high schools nationwide - this post is going to be about thermodynamics, and its relation to supramolecular bonds and medical implants.

In last week's post, we said that the construction of the machines was due to the supramolecular bonds found in rotaxane. Check out this video showing macroscopic self assembly molecules.

There are many constraints, however, to the making of these machines, and this is due to the supramolecular bonds. These machines require great precision, and while one may think that this is due to their small size or delicate material, it is actually due to the thermochemistry behind these bonds. These bonds require very little activation energy for formation, like other non-covalent bonds. As a result, the making of these machines requires great precision and accuracy, as this process can be extremely spontaneous. The importance of thermodynamics becomes more pronounced in biological systems. Because these systems often operate with a narrow temperature range, it is important that the supramolecular bonds are stable so molecules stay in their conformations and molecular mechanics can continue to occur. You can check out some interesting papers about the thermochemistry of supramolecular bonds here and here. Thanks for following.

Nano-Machines Mimic Muscles

In a recent paper, scientists from France's National Centre for Scientific Research (CNRS) reported that they were successful in the development of an artificial muscle construct.This innovative work, headed by Nicolas Giuseppone, a professor at the Université de Strasbourg, and involving researchers from the Laboratoire de Matière et Systèmes Complexes (CNRS/Université Paris Diderot) uses tens of thousands of individual molecular nano-machines. The nano-machines work together to extend and contract a polymer chain over a length of 10 micrometers. The main compound in the polymer chain is rotaxane, which is a molecule that is commonly studied with regard to molecular machine construction. 

Rotaxane is an example of a mechanically-interlocked molecular architecture. What this means is that rotaxane is compound that is a combination of molecules that are not connected by bonding but rather by geometry. An analogy, which is explains this is that of a key and a key chain; the keys are not directly attached to the key chain, yet the keys cannot be removed from the chain until the chain is broken. In this case, the blue part of the rotaxane, which is a dumbbell shaped molecule, plays the role of the key while the cyclobis macrocycle is the key chain.

Crystal Structure of Rotaxane with a Cyclobis Macrocycle

The French researchers were able to extend and contract the chain by varying the pH levels of the environment. A change in pH causes the thousands of individual components to either compress or elongate by one nanometer, and these changes in size in the individual molecules add up to cause a drastic change in the size of the polymer chain. This movement in the polymer chain is significant enough and easily controllable so the chain can be used to mimic the function of real muscles and can also function as a nano-scale mechanical machine.

Image depicting the contraction and expansion of the polymer chain in a way that mimics human muscle movement.

The way scientists were able to connect thousands of rotaxane together to form a polymer chain is through supramolecular bonding.  A supramolecular bond is an interaction between different molecules that is not based on a traditional “covalent” chemical bond but instead on what are known as “weak interactions”, thereby constituting complex molecular structures. Supramolecular bonding can consist of a variety of interactions like hydrogen bonding and van der Waals forces. The strength of supramolecular bonds ranges from very weak like hydrogen bonding to very strong like covalent bonding.  It is the supramolecular bond that connects all the elements in the polymer chain together and makes the contracting and extending of the chain possible. 

Gritty Graphene

Graphene: The gritty nanomaterial

Over the past few weeks, we have looked at various different nanomaterials that can serve as possible candidates for implants; from hydroxylapatite to silk, all these materials can be used to make significant upgrades on the current titanium implants in the medical field today. In this post, we will be looking at another nanomaterial - this time however, the nanomaterial is completely composed of carbon. Graphene will be the focus of this post today, as graphene is an extremely strong yet extremely thin material, as mentioned in the blog Graphene Mining. Graphene Mining goes on to mention that graphene is about 10 times stronger than titanium - you can check that out, along with some other interesting facts about graphene over here. Due to this fact and its size, graphene presents itself as another innovation in the field of implants.

An interesting article found by Graphene Mining talks about Mark Cheng, a scientist who wants to study the use of graphene as a material of implants.

New research aims to use Graphene to build better neural implants to treat blindness, spinal cord injury, etc. bit.ly/TBYLUE #greg
— Graphene Mining (@Chemblue1) December 2, 2012

Cheng is researching the possibility of neural implants made of graphene. The one important aspect of neural implants is the ability to send and receive electrical impulses, as neural implants are going to be used in the brain. Current implants, which are made of a combination of titanium and plastic as mentioned here (link), do not conduct electricity very well. Graphene, however, is an extremely good conductor of electricity, and this can be seen with some EChem (or electrochemistry). At the Harbin Engineering University, researchers have demonstrated the conductivity of graphene by producing a manganese dioxide-graphene composite through the following redox reaction.


The redox reaction used in the experiment.

Along with dissipating greater charge, graphene is also extremely thin and small, making it a lot easier to implant. With every innovation, there is a setback, and in this situation, graphene’s flexibility impedes it from being extremely effective. Graphene’s flexiblity makes it more difficult to implant into the cranium. Cheng, however, has devised an interesting solution; he suggests the use of a silicon backbone to make it easier to implant the graphene into the brain.

Graphene presents itself as an interesting alternative for neural implants. This follows from its flexibility, strength, conductivity, and size. This post, of course, could not have been possible without the blog Graphene Mining. Once again, take a look at their blog over here. Also, stay tuned for a post on their blog about nanoimplants as well. See you soon!

Implantable Silk Optics

In one of our earlier posts, we introduced you to the work of Fiorenzo Omenetto and a TED Talk he gave about the potential applications of silk in the medical industry and how silk can be used to fabricate better medical implants. Now, Omenetto and his team of researchers at Tufts University have created an silk optical implant.

A microscopic image of a silk optical implant embedded with gold nanoparticles

The optical implants are made of a purified silk protein and arranged in microprism array by pouring the solution of silk protein into molds of multiple micro-sized prism reflectors. After the cast solution dries, a silk sheet is formed that looks very similar to reflective tape. The benefit of fabricating silk sheets in the MPAs is that when the silk films are implanted into the body, reflect back photons that are ordinarily lost with reflection-based imaging technologies, which allows for enhanced imaging even in deep tissue. 

These silk optical implants, which are an improvement to current tissue imaging techniques, can do much more than simple providing imaging for doctors. The devices can be engineered to also administer therapeutic treatments to patients. The researchers are able to embed both gold nanoparticles and the cancer drug doxorubicin into the silk sheets to treat targeted parts of the body were the silk sheets can be implanted. The benefit of this is that it allows for the precise delivery of drugs while also providing a mechanism with which to monitor the body with. When silk sheet is no longer needed, it dissolved into the body, doing no harm because it is biocompatible.

For more information visit Fiorenzo Omenetto's website.

Do astronauts have doctors in space?

Unfortunately not. However, this is no longer an issue, thanks to Dr. David Loftus's invention of the NASA Biocapsule. The Biocapsule is a breakthrough invention that has the potential to serve a variety of purposes, ranging from treatment of astronauts from the dangers of solar radiation to terrestrial uses like chemotherapy and treatment of diabetes. Yahoo! News explains that it is a carbon nanotube-based implantable device, about the size of a pencil tip, that can sense conditions of the body and release a substance when it is needed.

How it's made
According to a video from the Space Biosciences Division at NASA Ames, the carbon nanotubes are developed in a solution, and a plastic mold is placed into the solution. The nanotubes stick to the exterior of the mold, forming the biocapsule's structure. The capsule is then slid off of the mold, filled with cells, and capped off utilizing either a protein glue or more nanotubes.

How it works
The cells in the Biocapsule secrete the substance that needs to be delivered to the body when a particular trigger activates them. Due to the strong nanostructure, the cells are secured within the capsule, but the carbon nanotubes are porous so that medicine can exit the capsule through diffusion across the capsule wall.

The energy needed for the cells to produce the therapeutic molecules is derived from the cells' own metabolism, which is supported by nutrients that are diffused into the capsule through the pores of the capsule wall. This allows the cells to last for months or even years.

To implant the device, a miniscule incision is made on the skin for each Biocapsule. The Biocapsules are then implanted under the skin, a procedure that only requires local anesthetic and one or two stitches to seal the wound. They are now ready to perform their function, as described above.


What's so great about it
The Biocapsule is cheap and can be easily produced, as shown in the video. It could also get rid of the need to constantly monitor the body, because it does the job for you by sensing irregularities in the levels of radiation or glucose or whatever it is engineered to detect. Once it detects abnormality, it dispenses medicine automatically. Each capsule is able to deliver many doses over the duration of several years. According to Fellow Geek, this implant has such high resilience that there is no known enzyme that can decompose the nanostructure. The nanostructure is inert, so the body does not react to it, allowing for high tolerance of the capsules by the body. The Biocapsule remains in the body after all the cells are used up, and may be eventually removed by a doctor.

Its uses



The original and main purpose of this device is to treat astronauts in the case of acute radiation exposure caused by "solar particle events," which are abrupt releases of severe radiation from the sun that can damage bone marrow and wipe out a person's immune system. The Biocapsule may be filled with cells that can sense elevated radiation levels and immediately dispense a hormone called Granulocyte colony-stimulating factor (G-CSF), which is already used to treat cancer patients receiving radiation treatment, to help protect the body.

The primary potential use of the implant on Earth is diabetes treatment. The capsule may be filled with insulin-producing islet cells that sense blood glucose levels and secrete insulin as needed. If this method was used, diabetes patients would not have to be concerned with getting shots or remembering to carry medicine everywhere. Many diabetes patients fall into comas or die while sleeping because they cannot monitor their blood sugar levels during that time. The Biocapsules function while patients are awake and asleep, so this problem would be eliminated.

Cancer treatment is a secondary application of Biocapsules on Earth. The capsule may contain chemotherapy medicine and be implanted directly into a tumor. This would minimize detrimental effects on surrounding healthy tissue and thus avoid the negative effects of chemotherapy.


This miniscule implant, the NASA Biocapsule, can release medicine by itself.

A Shrimple Solution

Previously on our blog, we mentioned the wonders of silk - a natural material that exhibits properties found in  nanomaterials. Scientists that are trying to make tougher nanomaterials are now looking at the structures of animals for inspiration. A finding over the summer has shown that due to its nanoscale structure, the mantis shrimp, otherwise known as Gonodactylus smithii, can strike prey with speeds, "matching that of a 5.56mm rifle."

A feature on USA Today even claims that club of a mantis shrimp can shatter a hole into aquamarine glass. Science Daily reports that Assistant Professor Ali Miserez lead a team that found that the unique structure of the mantis's claw makes it stronger than most ceramics out in the implant market now. Check out the original article over here. The following video illustrates the sheer strength of the shrimp's claw - the reasons behind this will be discussed a little later.

A video illustrating the awesome strength of the mantis shrimp.

Chitosan - an extremely long carbohydrate

This is an extremely important discovery, as it leads to many implications in the science of implants. Currently, a combination of titanium and polyethylene (aka plastic) is used in hip and other implants. This presents two problems. The first problem is that this combination of materials is, while not weak, not particularly strong. Also, since these implants are made of foreign materials, the body is more likely to reject them. Prof. Miserez's finding mollifies both these problems. The claw of the mantis shrimp is composed of hydroxylapatite, a strong calcium compound, and chitosan, a naturally occuring carbohydrate molecule, according to a Discovery News article. The hydroxylapatite allows for initial toughness, while the chitosan allows for more impact to be absorbed. The chitosan was found to be arranged like stacks of paper, thus effectively dissipating most of the impact incurred after the blow dealt by the mantis shrimp. The study of the shrimp's structure can lead to new and interesting innovations in the art of making ceramics. 

Brain Implants and Nanotechnology

The use of nanotechnology has enormous potential for brain implant devices. A breakthrough by biomedical and materials engineers at the University of Michigan has led to the development of a new nanotech coating for existing brain implant devices. The coating helps to greatly extend the operating life of many brain devices and potentially could aid in the treatment of deafness, paralysis, blindness, epilepsy, and even, Parkinson's disease. Many researchers have found in recent years, that paralyzed people can use their thoughts in conjunction with implanted electronics and a computer to control a wheelchair, and the folks at Michigan have found that their nanocoating increases the efficiency, effectiveness, and lifespan of these microelectrodes. This special coating is made from a electrically-conductive nanoscale polymer called PEDOT, a natural gel-like buffer called alginate hydrogel, and biodegradable nanofibers loaded with a controlled release anti-inflammatory drug. The PEDOT enables electrodes to operate with less electrical resistance so they can communicate with neurons better while the nanofibers and the alginate hydrogel work in tandem to make sure the body does not attack the coating because it is a foreign species and thus keeps the coating biocompatible.

The University of Michigan also another exciting development in regards to brain implants and nanotechnology. A team created a thin flexible device that is almost 10 times smaller than other current electrodes. The new electrode developed by the teams of Daryl Kipke, a professor of biomedical engineering, Joerg Lahann, a professor of chemical engineering, and Nicholas Kotov, the Joseph B. and Florence V. Cejka Professor of Engineering, is much more biocompatible than other larger microelectrodes. It is a thread of highly conductive carbon fiber, coated in plastic to block out signals from other neurons. The conductive gel pad at the end cozies up to soft cell membranes, and that close connection means the signals from brain cells come in much clearer.

An depiction of neurons. 

The device works similar to how the brain works because the carbon fiber is able to convert the movement of ions into the movement of electrons which allows for sharper electrical signals that can hone in on single neurons. This development represents a significant step toward the development of brain implant devices on the nanoscale that are in similar size to actual brain cells.

Interview with Fiorenzo Omenetto

Recently Fiorenzo Omenetto appeared on Public Radio Exchange for the Science Update. Have a listen below:

Silk in Medical Devices

In our last blog post, we examined the applications of the nanomaterials of liquorice. This post also deals with a well known material: silk. Silk is often recognized as a great textile, yet this material that has been around for centuries has very pertinent applications in the nanomaterials and medical implant industry. A recent Ted Talk by Fiorenzo Omenetto, a Professor of Biomedical Engineering at Tufts University, examines many of the attractive properties that silk has to offer, particularly its ability to be biocompatible and transmit light.



Omenetto envisions applications of silk that could revolutionize the medical industry. Silk fibers could carry light to places in the body for internal imaging, giving doctors the ability to perform diagnostic exams through very small openings in the body because the diameter of spider silk is a mere 5 microns think, 10 times thinner than human hair. Silk bandages equipped with electronics could be developed to monitor patients. Omenetto states that the best part about using silk is that "these materials are harmless so you can implant them." Couple this with scientists ability to use spider silk to fabricate electronic computer chips and you have an extremely powerful medical monitoring device.

Not only are device made out of silk biocompatible, but they are also programmable to decompose. Currently most medical implants need to be surgically removed after fulfilling their use. A team led by John Rogers at the University of Illinois Urbana-Champaign, created a special silk coating that would be able to dissolve in liquids. Because the material is non toxic, upon dissolving in a liquid environment like the human body, there would be no need for surgical removal and the risk of post-surgery infection would be reduced.

Although these applications of silk are sill not commercially feasible, Omenetto believes that in just a mere decade, silk will be the future of medical devices.


 

Liquorice in Nano-coating?

A recent study done by a team of researchers from Australia and Germany found a novel solution to a common problem in the medical field. The dilemma was that the biological components in medical implants are sensitive and can be damaged by harsh sterilization processes such as exposure to toxic gas or a blast of radiation. This would make the devices useless but sterilization cannot be avoided and is necessary to protect infection in patients when the devices are implanted. The research team discovered that a component in liquorice, glycrrhyzic acid, can be used to create a nano-coating on the surface of the medical device. The coating protects the bio-molecules from getting damaged by sterilization processes. It is unique in that it has no sugars, sugar-alcohol compounds or proteins that would hinder the biological activity of the device, unlike other stabilizing methods. The efficacy of this technique was tested by blasting a test device with radiation to completely sterilize it, resulting in no damage to the nano-coating and proteins and maintaining the function of the device. Now that the problem of medical devices containing biological components has been solved, the nano-coating can be used in the manufacturing of more effective biomedical devices.

So how exactly does the nano-coating protect proteins from radiation? Here is a diagram from the published article of what happens during the nano-coating process. (a) The “Y” shapes are proteins that are on the surface of a device. In (b), they are embedded with the nano-coating and dried. As seen in (c), the proteins are protected from radiation, which are represented by lightning bolt symbols. (d) The nano-coating is removed through rehydration. The gray oval shapes in (e) and (f) are the nano-coating that “stabilizes” the proteins by doing hydrogen bonding with the proteins and by replacing water. The coating ensures that radiation does not denature the proteins in the medical implant.

By: Soohee Lee and Olivia Park 

An illustration of the nano-coating process

Nanotechnology in Medicine

Here is an interesting article discussing the impact of nanotechnology on the medical field. Catharine Paddock, PhD defines nanotechnology in the following fashion:

“the manipulation of matter at the atomic and molecular scale to create materials with remarkably varied and new properties, is a rapidly expanding area of research with huge potential in many sectors, ranging from healthcare to construction and electronics.”

For the uninitiated, the nanoscale is incredibly small; one nanometer is approximately 3-5 atoms thick or about 40,000 times thinner than the human hair. Working at such microscopic levels gives scientists the ability to exploit interesting structures and properties of nanomaterials.  Such innovation technology is extremely promising for the medical industry; nanotechnology “promises to revolutionize drug delivery, gene therapy, diagnostics, and many areas of research, development and clinical application.”

Many of the applications of nanotechnology with regards to medical implants will be presented here as well as the concerns highlighted in the article about nanotechnology in general.

One use of nanotechnology is the fabrication of nanobots in the treatment of patients of various diseases. The primary benefit of nanobots is that it allows for the precise delivery of drugs. These nanobots bind to specific targeted molecules in the body and then release the drug they are carrying upon contact. Materials like gold have been researched and used for the fabrication of nanobots. An idea proposed by a MIT research team is to create nanomaterials that fabricate drugs at the site of the disease in the body. This solves the problem of drugs breaking down while being delivered to disease sites. 1

Like many other parts of science, fibers have recently been taken to the nanoscale as well. Fibers with “diameters of less than 1,000 nm” are referred to as nanofibers. Nanofibers have shown to have extremely important applications in “wound dressings, tissue engineering,” and medical implants as well. Until the past few years, synthesizing nanofibers has been a painstaking, time-consuming, and very expensive process. Researchers have, however, come up with a new method for developing nanofibers. The secret lies in the nickel nanoparticles - because of their structure, they can help grow nanofibers at high temperatures. Of course, in a modern-day lab setting, attaining these high temperatures is extremely cost-effective, and thus, making nanofibers is now a relatively cheap process.

Lead nanofibers have achieved a niche in the field of surgery, where surgeons are using lead nanofiber meshes to repair certain membranes found in the brain and spinal cord. For these situations, extremely small and not thick particles are needed. The applications can also be extended to fixing “hernias, fistulas, and other injuries.” Due to their versatility, nanofibers can be considered extremely important in the field of surgery and medical implants.

The future of nanotechnology in medical implants is not as rosy as it seems. There exist many concerns and obstacles regarding nanotechnology. The production costs of creating these unique nanomaterials are costly and cannot be adopted on a big manufacturing scale. The safety of nanomaterials has not been studied as extensively as other materials. Although the National Cancer Institute in the US states that most nanomaterials are less toxic than common household products, there still exists much ambiguity surrounding nanomaterials in general. There are concerns about what would happen to the human body if nanomaterials do not break down and dissolve as they were engineered to do.

Nanotechnology has the potential to revolutionize the medical industry despite some drawbacks and concerns about it. Stay tuned to our blog as we seek to document discoveries and innovations for nanotech medical implants.

Welcome to Our Blog!

C₆₀- a nanomaterial

Welcome to Yellow Five's blog! This is the place to find new information about the uses of nanotechnology in medicinal implants. We will be looking at various articles, and posting the most interesting ones here on this blog. So stay tuned, and follow us on Twitter @YellowFive. See you soon!