Shape-Memory Polymer Scaffolds

Researchers at Harvard University have recently come up with a method to create polymer scaffolding that can transport drugs and stem cells but doesn't have to be surgically implanted. Instead, it can be injected through a syringe and emerge in the body in the original shape it had because of shape-memory properties. They tested it using scaffolds in circle, heart, and star shapes, and found that it worked each time.

The actual chemistry behind the process of creating these scaffolds relates quite a bit to what was learned in class. The polymers undergo what is known as cryogelation, depicted in the figure below. First the polymer solution is prepared in the liquid phase. Since it is a solution, as we learned in class, the freezing point is going to undergo a depression so the mixture has to be frozen at a subzero temperature. Once frozen, polymerization occurs and ice crystallizes. Then the cryogel is left at room temperature, where it thaws and leaves behind a system with interconnected pores.

Note, however, that this polymerization only occurs in the first place due to the presence of intermolecular forces. The polymer being used is alginate, whose structure is shown below. Because of the hydroxyl groups, there are many polar oyxgen-hydrogen bonds, and the presence of ionized carboxyl groups means that hydrogen bonding will occur. This is what allows the polymers to cross-link so well and form the pores in the first place.

Without the fundamental concepts of intermolecular forces and solution composition as covered in class, these polymer scaffoldings would not even have been possible to make.

New Method to Revive Old Stem Cells

Stem cells are cells that are able to transform into cells of other types. This is particularly useful when trying to restore a part of the body internally, as they can continually divide in order to repair other cells. As stem cells grow older, however, their capability to maintain tissues declines. A new method was recently discovered that changes the stem cells so they behave more like younger stem cells, increasing their functioning ability. In particular, this method can help develop cardiac patches for those patients with damaged hearts from their own stem cells. This new procedure is specifically useful as the age of the patient will not affect the success of the stem cell restoration. 

However, in some stem cell therapies, such as those involving bone marrow, there is always a risk of patient rejection. As we discussed in one of our Diigo posts, scientists often use cells from a patient's own body to resolve this issue. We believe that this would also be helpful as patients would not have to wait around for another individual's organ or tissue donations; rather, they would have immediate access, as cells are from their own body. However, for older patients, the stem cells have become aged and function less than younger cells. Using this new technique, the stem cells from elderly patients can be utilized without being rejected.

This method was created by Milica Radisic and Dr. Ren-Ke Li, two researchers. They created conditions similar to the aged stem cells in tissue cultures, referred to a "micro-environment." In this micro-environment, which the heart tissue would grow in using stem cells from elderly patients. Various factors causing cell proliferation , or the increase in cell numbers, are added to the cell cultures. These infusions caused aging factors to be reduced and cells to be restored to younger versions. In particular, molecules such as p16 and RGN were infusions that caused this to occur. 

The molecule "p16" is a gene that is inactivated when cancers are present in humans. Similar to our topics in biology last year, genes can be inactivated or activated to cease or continue a function. In this case, c ells are usually limited in their growth through the activation of p16, but when inactivated, p16 actually causes tumors to form. Tumor suppression occurs through protein-protein interactions with p16. Specifically, p16 binds to CDK4, another gene, which causes it to be active.

The structure of p16

The bonding that takes place between p16 and CDK4 is of Intermolecular Forces (IMFs). In particular, when CDK4 bonds with other genes, hydrogen bonding networks are created. As we have discussed in class, hydrogen bonds are attractive forces between a hydrogen and an electronegative molecule., usually of a nitrogen, oxygen, or fluorine atom. The picture above shows the large number of hydrogen atoms in the structure of p16. Almost all of these hydrogens are attached to an N or an O, two atoms that are also abundant in p16's structure. This shows that hydrogen bonds exist in p16. P16 is not very structurally stable, particularly due to its "highly dynamic structure as measured by ANS-binding, NMR hydrogen-deuterium exchange, and fluorescence." Because of its weak structure, p16 also self associates and forms dimers. The Kd value of the molecule is only 270 microM for p16. Kd is the equilibrium dissociation constant of products over reactants in the reaction A + B ↔ AB. As discussed last year, it is a specific type of equilibrium constant, K, and is the reciprocal of Ka, the equilibrium association constant. 

In the future, this method can be utilized in many applications. When the stem cells in elderly patients start decreasing in function, they will be revived using this "fountain of youth" technique. Damage caused by heart attacks will be repaired, and defects such as aneurysms can be fixed as well. Although this discovery can be very useful, it might also have several drawbacks. There has always been debate over the moral issues of stem cells. With this discovery, scientists would be tampering with the naturally occurring chemicals, bonding, and genes in the body. Perhaps, for many people, this new method would not be a chemical wonder, but more of a manipulation of nature. 

http://www.newstrackindia.com/newsdetails/2012/11/28/373--Fountain-of-youth-technique-may-help-create-heart-patches-from-old-cells.html

Silk Hearts

Tying in with what we've learned in class, this article from Science Daily explains how silk from a Tasar Silkworm can be used as a scaffold for heart tissue. In other words, how they can use this silk to replace damaged heart cells that are unable to regenerate. They are hoping that this artificial tissue can restore total cardiac function in humans.

Penny-sized silk discs used for heart scaffolding.

These types of studies are so important because, throughout evolution, the heart has lost all regenerative abilities. So when people have heart attacks, all of the cardiac cells that die are lost and cannot be replaced by the heart itself. These studies are conducted to test different types of materials that can patch these dead cardiac muscles. One of their main issues is trying to reconstruct this three-dimensional structure.

Various other materials have failed to work because they were too brittle, rejected by the immune system, or did not allow the muscle cells to adhere with the fibers. Fortunately, researchers are starting to believe that this silk can be a viable material for this heart operation.

The silk has a protein structure that is able to adhere strongly to the heart muscle cells. The coarser material allows the cells to grow and form three-dimensional structures. The re-patched rat heart was able to beat as if it were healthy after being patched with the silk. This is certainly a promising sign for the future and is an indicator that silk can be very successful.

 As the figure to the right demonstrates, the structure of the silk in the Tasar silkworm is very similar to that of spider silk as discussed in a previous blog post, which is what lends it its adhesive properties.

The silk itself is composed of highly crystalline B-sheets crosslinked with less-ordered B-sheets. As discussed in class, the crystalline structure of the more ordered B-sheets allows the atoms to be more tightly connected in a pattern, whereas the less-ordered sheets have an amorphous structure. Furthermore, the pleated B-sheets exhibit hydrogen bonding. As we also learned in class, this is the strongest intermolecular force and results in the interlocking strands. It is because of these properties that the silk is so strong and so capable of adhering tightly to the human body.

Unfortunately, they have been unable to obtain the necessary amount of cardiac cells for the starting material in humans. All tests were conducted on rats and were generally successful. On humans, however, much work still needs to be done. Scientists are in the process of using stem cells in place of these cardiac cells, but trials are still in the early stages.

Tissue engineering is a very important field for improving the overall life of humans. In my opinion, the studies conducted to improve the heart are some of the more important due to the vital role that the heart plays, as well as the fact that heart issues are very common. Any way that scientists can help this problem would be very beneficial to all that suffer from heart conditions.