Department of Mechanical Engineering
Research Areas: Biomedical Micro- and Nanotechnologies (Bio-MEMS), Tissue Engineering, Organs-on-Chip, and Microfluidics
What does a spider have to teach us about engineering replacement human tissues? Quite a lot. At least that’s what Dr. Mohsen Akbari, a biomedical engineer at the University of Victoria, would argue.
Dr. Akbari began his career in the auto industry, but quickly found himself transitioning to a world of research that held more meaning for him; a field that lies at the interface of medicine, cellular biology, biomaterials and mechanical engineering.
“One of the reasons I am interested in biomedicine and tissue engineering is for personal reasons,” says Akbari. “I lost my mother to breast cancer.”
Tissue engineering. Akbari is now an assistant professor and researcher with UVic’s Department of Mechanical Engineering. His focus is on the biofabrication of engineered tissue substitutes using fiber-based technologies.
Tissue engineering has countless applications, from regenerative medicine to fundamental research. Lab-made tissue substitutes that mimic the structural and functional properties of real human tissues can theoretically be used to repair damaged spinal cords, construct new organs for transplant, and act as experimental models on which to test a host of pharmaceutical drugs.
Hydrogel microfibers. Akbari uses microfluidics to make hydrogel microfibers, the building blocks of 3D tissue constructs. A single fiber is made up of a synthetic polymer core coated with a hydrogen layer that may contain anything from live cells to drugs, hormones and other microparticles.
“The idea of fiber spinning and microfluidics comes from spiders,” says Akbari. “We looked at the way spiders spun silk and then adopted a similar process.”
Microfibers are made by drawing a ‘sticky’ (thanks to the presence of a cross reagent) polymer core through reservoirs of cell-laden prepolymers. Literally meters upon meters of any given fiber — no larger in diameter than the width of a human hair — can be rapidly manufactured.
“Imagine spools of different fibers,” says Akbari, “which can then be assembled into different tissues using textile technology.”
Hydrogel fibers are advantageous because their composition and properties can be designed to preference. The hydrogel’s that Akbari works with are made from natural materials, such as gelatin, collagen or alginate, and are made-to-order. One hydrogel might contain endothelial cells (for engineering capillaries and blood vessels) while another might be laden with conductive cells (for use in heart or neural tissue). Drug-embedded fibers can even be designed to dissolve over time, facilitating a controlled and steady rate of release.
Akbari is particularly interested in the processing side of fiber development. He has successfully manufactured a host of different fibers with distinct properties — rigid or flexible, soft or hard, hollow or solid, pure or composite — each one designed for a specialized function.
Akbari is currently studying conductive fibers, which are ideal for neural tissue engineering, as part of a collaborative project he is working on with fellow UVic biomedical engineer, Dr. Stephanie Willerth. “I’m really excited to put some of the stem cells and aggregates from Dr. Willerth’s lab into these fibers and see how they affect cell differentiation,” says Akbari.
Fiber assembly. Another one of Akbari’s key areas of research is in developing functional 3D tissue constructs by bundling different types of hydrogel fibers together in different ways. He employs two very different microengineering techniques to create tissues with distinct mechanical properties: textile technology and bioprinting technology.
“Imagine that you want to make a blood vessel,” says Akbari. “You can have your endothelial cells in one fiber, smooth muscle cells in another fiber, and then you just arrange the fibers in a way that you can make large-scale or small-scale blood vessels.”
Akbari has already used textile technologies to manually produce strong products that are made up of interlocking fibers of various patterns that include: braiding, weaving, and embroidering. This method of fiber assembly is ideal for replacement tissues that must be able to withstand a lot of stress.
Akbari is also working collaboratively with UVic colleague, Dr. Nick Dechev, to investigate different platforms for fiber production through 3D printing. Bioprinting generates tissues that are composed of successive layers of fibers, rather than interlocking fibers, and is ideal for manufacturing soft or stretchable tissues.
“We’ve made these constructs manually,” says Akbari, “but what I want to do now is make the machinery to do this. When you make things manually you don’t have very good control of constructs. I want to automate it so we can have more consistent and reproducible results.”
PH-sensitive wound dressing. Akbari’s team has already successfully applied these techniques to develop a novel dermal patch, or wound dressing, which is the focus of a 2015 article entitled, Flexible pH-Sensing Hydrogel Fibers for Epidermal Applications. Composed of malleable microfibers, the patch contains pH-sensitive dyes that respond to the physiological environment of the underlying skin. Because wounds heal best in an acidic environment, clinicians can use the patch’s pH distribution map to monitor wound healing.
Organ-on-chip. Akbari is also interested in the design and development of cell-based microarray platforms, which can be used to conduct fundamental studies, including high-throughput drug screening.
These platforms, colloquially known as ‘organs-on-chip’, are essentially a conglomeration of different fibers that have been meticulously assembled into a tiny model organ (often no more than a few mm’s in size), whose structure and function mimics that of a genuine organ in its natural environment. These engineered organs can be kept functional over extended periods of time, allowing for long-term, reproducible and highly controlled studies.
“The ultimate goal is to develop what pioneers call a ‘human-body-on-a-chip’, to bring the human body in vitro, to use human cells, biomaterials and microfluidics technology to mimic what really happens in the human body,” says Akbari. “Then, instead of testing a drug on a real human, we test it on a human-like in vitro system.”
The bonus here is two-fold. Animal studies that are currently used for clinical trials are expensive, unreliable and plagued with ethical issues. “‘Organ-on-chip’ will eventually replace animal studies,” says Akbari.
Furthermore, by shrinking everything down onto a microscale, researchers minimize study costs and maintain a high degree of experimental control. “We can control the environment at the cellular level,” says Akbari, “so we can closely mimic what happens in the human body.”
Cancer research. Akbari is currently studying the systemic effects of breast cancer drugs by creating an experimental system that couples a tumor-laden ‘breast-on-chip’ with a healthy ‘liver-on-chip’. This research is particularly important in light of experimental drug therapies that employ cancer killing-nanoparticles that are designed to target the tumor but also end up accumulating in the liver.
“My goal is to come up with something that can have a huge impact in people’s lives,” says Akbari. “Back then I couldn’t do anything for my mom, but I think now, I can do something for other people.”