Health and Medicine Technology

Implantable Devices Used for Better Drug Testing Techniques

Tissue-On-A-Chip

Researchers that have been funded by the National Institute of Biomedical Imaging and Bioengineering (or NIBIB) have built a new type of tissue chip that works as a much better representation of natural human tissue. By engineering the chips as a silk gel, the researchers were able to fix many problems with current devices used today. The new chips can be more widely used for drug testing and have the potential to someday become an implantable form of treatment.

Tissue chips work by mimicking both the anatomy and the physiology of a tissue or organ, making it possible to test treatments in a lab far more accurately than using cells growing in a single layer inside a dish. In order for tissue to be engineered outside the body, the cells need a three dimensional structure which they can grow within. These scaffolds are most often made out of polydimethylsiloxane (PDMS), which is a silicon-based polymer and is made up of microfluidic chambers running through them.

These systems have many advantages. Some are wonderful for developing and testing treatments, others are great for letting living cells embed within them and others are perfect for replicating a variety of tissue types. Other systems can be implanted within the body as a part of a treatment program; these devices will then decompose when they are no longer needed.

silk chip
The alkaline phosphatase enzyme is injected into the silk-based chip and remains biologically active (yellow) as it dilutes into the silk hydrogel after 5 minutes (left) and 30 minutes (right).
(Image Credit: Zhao, et al. Biomaterials, Jul 2016 Elsevier)

Unfortunately there is not a biomaterial that can do all of the above. In order to create a system that addressed all of these needs, researchers started using silk which is a naturally derived protein with unique properties that have a handful of benefits: they offer different levels of stiffness to match the tissue being targeted, offer long-term stability in a wide range of conditions but can fully degrade over a specific period of time and provide a transparency that allows researchers to observe biological processes.

Rosemarie Hunziker, program director for Tissue Engineering in NIBIB say silk is biocompatible so you can use it even inside the body, and it can be programmed to dissolve safely over time. This may even be an improved design that enables researchers to built little micro-tissues and make them implantable.

Department of Biomedical Engineering at Tufts University in Medford, Massachusetts researchers have developed a microfluidic device by mixing silk with a gel solution and casting it into a mold. This built a rectangular block of silk hydrogel with a three dimensional network of channels running through it. Mechanical valves were added in order to help control the flow through the channels, which could be switched on and off based on the air pressure within the chambers.

In living organs and tissues, interactions among other proteins, cells and enzymes happens inside the tissue as well as on the surface of the channels. Modeling this involved embedding living cells and active enzymes within the gel while it’s made. The difficult conditions call for the creation of PDMS kill and deactivate cells and enzymes. Since silk hydrogel can be made at ambient temperatures and under relatively gentle controls, it can include cells and enzymes within the gel, which means better replicate living tissue.

fibroblast
3D image of skin cells that were successfully grown in the silk-based hydrogel. (Image Credit: Siwei Zhao)

The silk gels were able to withstand a wide range of environments which included dramatic changes to fluid pH or salinity without altering their size or shape. The stiffness of the gel could also be manipulated to match the properties of the target tissues. The gels were also clear, making analysis very easy.

Testing potential drugs is most likely going to be the primary application of the new silk system, but researchers are also excited about the possibility of someday being able to grow tissues on chips that can be put directly into the body. Senior author of the paper, David Kaplan explains that silk takes you to the next level because it can be implanted and fully reabsorbed in vivo.

Kaplan says silk is pretty unique in the ability to integrate everything into one material system. Now we can optimize systems in vitro and directly translate that in vivo to look at tissue regeneration. He says he does not know of any other system with the versatility that can do all of that. In the past, Kaplan has used silk to solve other biomedical engineering problems. He has used it to make models of brain tissue and bone marrow as part of surgical implants to heal broken bones, and as a method for keeping antibodies and vaccines stable at room temperatures. He calls it pretty rare when you hit a roadblock that cannot be overcome with silk as the base material.

Silk is a fairly universal material and the team is hopeful that it has now officially been moved out of the textile world and into the biomaterials and medical worlds. When compared to other polymers that have been tested, silk is very well studied. A lot is already known about how it reacts inside the body. Hunziker says that in terms of developing silk-based tissue implants it is a lot like starting a relay race on the last lap instead of from the beginning.

The full study was published in Biomaterials journal.

Save