Showing posts with label organ implants. Show all posts
Showing posts with label organ implants. Show all posts

Thursday, May 28, 2015

Spinning a new version of silk


Microscope images of lab-produced fibers confirm the results of the MIT researchers' simulations of spider silk. At top are optical microscope images, and, at bottom, are scanning electron microscope images. At left are fibers 8 micrometers across, and, at right, are thinner, 3 micrometer fibers.
Microscope images of lab-produced fibers confirm the results of the MIT researchers' simulations of spider silk. At top are optical microscope images, and, at bottom, are scanning electron microscope images. At left are fibers 8 micrometers across, and, at right, are thinner, 3 micrometer fibers.
Courtesy of the researchers

Simulations and experiments aim to improve on spiders in creating strong, resilient fibers.
After years of research decoding the complex structure and production of spider silk, researchers have now succeeded in producing samples of this exceptionally strong and resilient material in the laboratory. The new development could lead to a variety of biomedical materials — from sutures to scaffolding for organ replacements — made from synthesized silk with properties specifically tuned for their intended uses.
The findings are published this week in the journal Nature Communications by MIT professor of civil and environmental engineering (CEE) Markus Buehler, postdocs Shangchao Lin and Seunghwa Ryu, and others at MIT, Tufts University, Boston University, and in Germany, Italy, and the U.K.
The research, which involved a combination of simulations and experiments, paves the way for “creating new fibers with improved characteristics” beyond those of natural silk, says Buehler, who is also the department head in CEE. The work, he says, should make it possible to design fibers with specific characteristics of strength, elasticity, and toughness.
The new synthetic fibers’ proteins — the basic building blocks of the material — were created by genetically modifying bacteria to make the proteins normally produced by spiders. These proteins were then extruded through microfluidic channels designed to mimic the effect of an organ, called a spinneret, that spiders use to produce natural silk fibers.
No spiders needed
While spider silk has long been recognized as among the strongest known materials, spiders cannot practically be bred to produce harvestable fibers — so this new approach to producing a synthetic, yet spider-like, silk could make such strong and flexible fibers available for biomedical applications. By their nature, spider silks are fully biocompatible and can be used in the body without risk of adverse reactions; they are ultimately simply absorbed by the body.
The researchers’ “spinning” process, in which the constituent proteins dissolved in water are extruded through a tiny opening at a controlled rate, causes the molecules to line up in a way that produces strong fibers. The molecules themselves are a mixture of hydrophobic and hydrophilic compounds, blended so as to naturally align to form fibers much stronger than their constituent parts. “When you spin it, you create very strong bonds in one direction,” Buehler says.
The team found that getting the blend of proteins right was crucial. “We found out that when there was a high proportion of hydrophobic proteins, it would not spin any fibers, it would just make an ugly mass,” says Ryu, who worked on the project as a postdoc at MIT and is now an assistant professor at the Korea Advanced Institute of Science and Technology. “We had to find the right mix” in order to produce strong fibers, he says.
Closing the loop
This project represents the first use of simulations to understand silk production at the molecular level. “Simulation is critical,” Buehler explains: Actually synthesizing a protein can take several months; if that protein doesn’t turn out to have exactly the right properties, the process would have to start all over.
Using simulations makes it possible to “scan through a large range of proteins until we see changes in the fiber stiffness,” and then home in on those compounds, says Lin, who worked on the project as a postdoc at MIT and is now an assistant professor at Florida State University.
Controlling the properties directly could ultimately make it possible to create fibers that are even stronger than natural ones, because engineers can choose characteristics for a particular use. For example, while spiders may need elasticity so their webs can capture insects without breaking, those designing fibers for use as surgical sutures would need more strength and less stretchiness. “Silk doesn’t give us that choice,” Buehler says.
The processing of the material can be done at room temperature using water-based solutions, so scaling up manufacturing should be relatively easy, team members say. So far, the fibers they have made in the lab are not as strong as natural spider silk, but now that the basic process has been established, it should be possible to fine-tune the materials and improve its strength, they say.
“Our goal is to improve the strength, elasticity, and toughness of artificially spun fibers by borrowing bright ideas from nature,” Lin says.  This study could inspire the development of new synthetic fibers — or any materials requiring enhanced properties, such as in electrical and thermal transport, in a certain direction.
“This is an amazing piece of work,” says Huajian Gao, a professor of engineering at Brown University who was not involved in this research. “This could lead to a breakthrough that may allow us to directly explore engineering applications of silk-like materials.”
Gao adds that the team’s exploration of variations in web structure “may have practical impacts in improving the design of fiber-reinforced composites by significantly increasing their strength and robustness without increasing the weight. The impact on material innovation could be particularly important for aerospace and industrial applications, where light weight is essential.”
The research was supported by the National Institutes of Health, the National Science Foundation, the Office of Naval Research, the National Research Foundation of Korea, and the European Research Council.

Wednesday, August 21, 2013

An Organized Approach to 3D Tissue Engineering

IBN’s novel technique brings researchers closer to viable organ implants

Researchers at the Institute of Bioengineering and Nanotechnology (IBN) have developed a simple method of organizing cells and their microenvironments in hydrogel fibers. Their unique technology provides a feasible template for assembling complex structures, such as liver and fat tissues, as described in their recent publication in Nature Communications1.
According to IBN Executive Director Professor Jackie Y. Ying, “Our tissue engineering approach gives researchers great control and flexibility over the arrangement of individual cell types, making it possible to engineer prevascularized tissue constructs easily. This innovation brings us a step closer toward developing viable tissue or organ replacements.”
IBN Team Leader and Principal Research Scientist, Dr Andrew Wan, elaborated, “Critical to the success of an implant is its ability to rapidly integrate with the patient’s circulatory system. This is essential for the survival of cells within the implant, as it would ensure timely access to oxygen and essential nutrients, as well as the removal of metabolic waste products. Integration would also facilitate signaling between the cells and blood vessels, which is important for tissue development.”
Tissues designed with pre-formed vascular networks are known to promote rapid vascular integration with the host. Generally, prevascularization has been achieved by seeding or encapsulating endothelial cells, which line the interior surfaces of blood vessels, with other cell types. In many of these approaches, the eventual distribution of vessels within a thick structure is reliant on in vitro cellular infiltration and self-organization of the cell mixture. These are slow processes, often leading to a non-uniform network of vessels within the tissue. As vascular self-assembly requires a large concentration of endothelial cells, this method also severely restricts the number of other cells that may be co-cultured.
Alternatively, scientists have attempted to direct the distribution of newly formed vessels via three-dimensional (3D) co-patterning of endothelial cells with other cell types in a hydrogel. This approach allows large concentrations of endothelial cells to be positioned in specific regions within the tissue, leaving the rest of the construct available for other cell types. The hydrogel also acts as a reservoir of nutrients for the encapsulated cells. However, co-patterning multiple cell types within a hydrogel is not easy. Conventional techniques, such as micromolding and organ printing, are limited by slow cell assembly, large volumes of cell suspension, complicated multi-step processes and expensive instruments. These factors also make it difficult to scale up the production of implantable 3D cell-patterned constructs. To date, these approaches have been unsuccessful in achieving vascularization and mass transport through thick engineered tissues.
To overcome these limitations, IBN researchers have used interfacial polyelectrolyte complexation (IPC) fiber assembly, a unique cell patterning technology patented by IBN, to produce cell-laden hydrogel fibers under aqueous conditions at room temperature. Unlike other methods, IBN’s novel technique allows researchers to incorporate different cell types separately into different fibers, and these cell-laden fibers may then be assembled into more complex constructs with hierarchical tissue structures. In addition, IBN researchers are able to tailor the microenvironment for each cell type for optimal functionality by incorporating the appropriate factors, e.g. proteins, into the fibers. Using IPC fiber assembly, the researchers have engineered an endothelial vessel network, as well as cell-patterned fat and liver tissue constructs, which have successfully integrated with the host circulatory system in a mouse model and produced vascularized tissues.
The IBN researchers are now working on applying and further developing their technology toward engineering functional tissues and clinical applications.