Knight Cancer Institute Building Biofabrication Hub

Photo: Ford, Brad

Growing mini-organs for research to unlock the mysteries of cancer and other human diseases. Engineering artificial but living tissues for transplant. These are some of the applications of biofabrication — and researchers at the OHSU Knight Cancer Institute have secured more than $1 million to equip and expand a newly formed Knight Cancer Precision Biofabrication Hub.

Located in the Knight Cancer Research Building on Oregon Health & Science University’s South Waterfront campus, the hub is off and running with biomedical engineering and cell biology experts collaborating on projects.

“Now we have these additional funds to equip the hub with state-of-the art technologies,” said its director, Luiz Bertassoni, D.D.S., Ph.D. “The real focus is to recreate cancer tissues using these fabrication techniques. This will let us dissect the complexities of cancers and understand the contribution of each one of these cells and tumor building blocks.

“It’s almost as if you had a big puzzle — and cancer is absolutely a big puzzle — and you can now separate each one of those pieces and see what each one of those pieces are doing.”

The M.J. Murdock Charitable Trust contributed half the funding, which was matched by awards put together by the OHSU Knight Cancer Institute, the OHSU School of Medicine, and Bertassoni, an associate professor in the OHSU School of Medicine, Division of Oncological Sciences, and a member of CEDAR, the Cancer Early Detection Advanced Research Center in the Knight Cancer Institute.

3D-printing tissue to understand cancer

Knight Cancer researchers are using lab-grown organoids and other biofabricated models to explore fundamental disease processes with more focus and flexibility than is possible with animal models or cultures of cells growing in a flat plastic dish.

Organoids are tiny, three-dimensional constructs grown from adult human stem cells. They can be engineered to replicate much of the complexity of a human organ. 3D printers — another tool of choice to fabricate tumors in the hub — can deposit living human cells, layer upon layer, to form tissues composed of many cell types. Within these bioprinted tissues, cancer cells can grow and exchange signals with other cell types. Together they mature, secrete extracellular matrix — or the proteins and molecules that give structure to cells — and self-organize to form features typical of real tumors, such as networks of blood vessels.

Organs-on-a-chip, which are also frequently used by engineers to study human biology, are microchips that simulate organ structure and function. Cells, air and fluid are transported by the chip’s grooves and channels and can build an entire interconnected vascular network with patient cells and flow tumor cells to predict what they do in the body.

“We can see the cells travel and metastasize before our eyes,” Bertassoni said. “This gives a lot of power in understanding cancer biology.”

The approach is particularly important for early detection research because of the limitations of using animal models to study how human cancers grow and turn life-threatening.

“We’d like to go even earlier and ask what cells are predisposed to developing into a tumor, what is setting them up for cancerous growth?” said CEDAR Co-director Shelley Barton, Ph.D. “With biofabrication, we can get as close as possible to human tissue, and then alter different variables — if I take this away or take that away, can I stop the tumor from developing?”

Building bone

Among other projects, Bertassoni’s team has developed a bone replacement material that can be injected into bone defects to form a scaffold for bone regeneration. By approximating the cellular, structural and chemical composition of native bone, the engineered material promotes native-like mechanisms of bone formation, the researchers reported in April in the journal Advanced Healthcare Materials .

Using a rat animal model, Bertassoni’s team showed that bone repair stimulated by their injected biomaterial mimicked the architecture of native bone down to its microscopic crystal structure. In the naturalistic but engineered microenvironment, both the implanted stem cells and the host animals’ stem cells contributed to the regeneration of mature bone tissue.

Key to this work is its potential to treat bone injuries without invasive surgery or having to harvest bone from another anatomic site. The material also stimulates bone repair without the severe side effects of competing, noninvasive methods that require recombinant growth factor.

Barton said the Precision Biofabrication Hub fits well with the work underway at CEDAR. “And Luiz is a really good mentor of trainees,” she added. “This hub is an inviting opportunity for grad students and postdocs to come build an organ from the ground up.”

Source: OHSU

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