In the silk they found proteins that are used to repair from bones to vessels capillaries and tendons. The cocoons that the worms make contain proteins that can be used as biomaterials.
about 5000 years ago The Chinese discovered the secret of silkworms and were able to separate their filaments to create threads capable of turning dreams into riches. With this milestone, the Chinese empire obtained an exchange value that would unite the world on his famous silk road. But there were still more secrets. These filaments have almost magical properties. For example, they offer resistance that exceeds steel.
Discovering how nature had managed for such a feat provides tools to obtain a material whose implications go beyond fabrics or anything that was thought of in the ancient world. However, the idea of using silk in medicine was anticipated to heal wounds and a few decades ago it was used as thread for sutures. The ancients could not think of disciplines such as bioengineering, in which they try to rebuild the body using techniques that bring together various branches of science such as physics, biology, computing, and chemistry. Silk is now seen as a key building block for biotech innovation.
PIONEERS
Research on the properties of silk is led by the Department of Bioengineering directed by Dr. David Kaplan at Tufts University found in Boston, Massachusettsprecisely in the area where they are also Harvard and MIT. Boston is a world benchmark in Biotech companies given its strong academic presence and government support for startups.
“When there is a wound, if it is deep enough, the body loses the ability to regenerate. We now know how to work with stem cells to induce them to differentiate into different tissues. In addition to providing them with the chemical signaling to promote their differentiation, we must confront them with information of the 3D environment that we want it to regenerate. In the case of bone tissue, for example, it is not just a matter of having a cell to make a bone, but also regenerating the shape of the bone”, points out Valeria Bosio, a Conicet researcher, awarded at the prestigious MIT, and director of the BIOMIT Lab at the University of La Plata.
The biomaterials revolution it is changing to focus on finding tools within nature itself. Specialists who work with titanium or other types of alloy bone prostheses generally speak of biomaterials when referring to any material that does not generate an immune response and is biocompatible. “But now we consider biomaterials to be those that come from nature such as macromolecules, be they proteins, lipids or polysaccharides. These molecules can be used as supports for cell growth”, comments Bosio.
scaffolding
Just as to build a building a structure is needed such as the beams that support the rest of the materials, in the human body various types of scaffolding are created that enable the formation of different organs and tissues such as bone. When an illness or accident alters these structures, they are unable to regenerate on their own. The scientists discovered that the silkworm created the basic ingredient to be able to design the supports that allow the cells to be routed to recreate the missing information and thus
bioinks
By separating the silk proteins and bringing them to a liquid solution, bio-inks can be created to design capillaries. restore lost tissues where they belong.
The silk is secreted by the worm in threads that can reach 1,500 meters and consists of two proteins, fibroin and sericin. “We mainly concentrate on the fibroin that we obtain as a solution according to protocols acquired in Boston with the world authority on the matter: Dr. David Kaplan and with whom we currently maintain collaborations between our laboratories”, says Bosio enthusiastically.
Being able to go from silk to a protein solution, that is, to a liquid,
it has its biochemical complexities, but once it is achieved it can be manipulated into various kinds of shapes. The main advantage of fibroin is that it is a biocompatible but also degradable material. “What one wants is for the cells to recreate the necessary structures, that is, their own extracellular matrix. With this support we help them to do so, since the cells fill and replicate them, but then we look for the support designed by us to disappear and the natural one remains. With fibroin we have that: a material that biodegrades, but remains long enough to help us recreate extracellular structures.”
REGENERATION
The potential applications depend on the type of structures to be created and in this the researchers design all kinds of new solutions. “We specialize in bone tissue, so we use interconnected pore structures. We can first simulate everything virtually, use artificial intelligence mechanisms to understand particular bones and thus generate fibroin-based scaffolds personalized to each patient. The idea is that this structure replaces part of the bone that is regenerating thanks to the support that we recreate with the biomaterial. Of course each application has its challenge in how these proteins are used. In our case, we use microparticles of calcium carbonate that help the cells to generate bone tissue”, comments Bosio.
Once you have the fibroin solution, a kind of honey, the techniques allow the development of other structures besides the sponges. Films, solid blocks, capillaries, and particles, among others, can be designed. It is about generating structures that allow the proliferation of cells to respond to various pathologies. For example, from particles it is possible to create bioinks with very diverse applications, such as generating blood vessels. One technique for this type of fabric consists in the use of a filament that as it rotates, the bioink is deposited on it. Then that bioink gels, the filament is removed and the structure remains on which cells will grow to generate a capillary vessel. The technique even makes it possible to make capillaries with several different diameters in addition to controlling their porosity and elasticity.
One of the most recent applications is the repair of tendons that usually present great difficulty. Tendon injuries have long, difficult treatments and often are incomplete in their healing process. Tendons are bands of fibrous connective tissue that attach muscle to bone. In other words, they are soft tissues connected to something rigid like a bone and that creates a complex and very specific structure. After an injury, this structure is altered and excessive healing causes its biomechanical properties to be lost. At the Terasaki Institute in Los Angeles, researchers published a method based on the silkworm in the Small journal. It is about using fibroin together with a moisturizing gel known as GeIMA to build a scaffold through which stem cells are directed towards the tendon and repair it, recovering its normal elasticity. Healing also occurs in a more accelerated way. There are many potential applications and this only from a protein.
The journey to the stars of the protein universe is full of challenges. Out there are millions of proteins created by nature. Fortunately, some captains like Valeria Bosio got on the ship to cross borders and go as far as human beings have never gone.
by Pablo Wahnon
