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Chemical and Biomolecular Engineering

Chemical and Biomolecular Engineering faculty member Brendan Harley and a team of researchers from the Carl R. Woese Institute for Genomic Biology’s Regenerative Biology and Tissue Engineering theme were awarded a National Science Foundation grant that will provide funding for a new 3D-bioprinting instrument.

The Major Research Instrumentation grant will fund the purchase of an EnvisionTEC 3D-Bioplotter, a bioprinting system that is essentially a 3D printer for tissues.

Much of the research in the Regenerative Biology and Tissue Engineering (RBTE) theme involves developing approaches to regenerate tissues in order to address problems of human health. But this is not a simple task, considering human tissues are all uniquely complex.

Bioprinting, which uses 3D printing technology to create cell patterns and fabricate biomaterials, will allow researchers to print materials that closely resemble human tissues.

Unlike many 3D printers, which print metals or other hard materials, this bioplotter will let researchers print a wide variety of materials — including materials that are similar in consistency to toothpaste, as well as materials that are the size of human hair or smaller.

“This bioplotter really allows us to do all that,” said Brendan Harley, Associate Professor of Chemical and Biomolecular Engineering and theme leader. “It really lets us open up the toolbox of the materials we can use.”

The bioplotter will be housed within IGB as a shared-use facility that will be accessible to researchers across campus.

Several research efforts at the IGB and the University of Illinois are dedicated to developing tissue engineering solutions that could impact a range of important healthcare issues such as cancer, stem cell behavior and more.

Harley hopes researchers will look to the IGB and the RBTE theme as a hub for tissue engineering on campus.

He said 3D bioplotters have finally become capable of reliably printing at the scale needed to produce complex tissues, and with the acquisition of this printer, IGB will be at the forefront of tissue engineering research.

“We’re going to be able to do some really exciting new work,” he said. “Everything’s in place to really attack big, challenging problems.”

By Emily Scott, IGB Science Writer and Outreach Specialist

(left) Ji Sun (Sunny) Choi, postdoctoral research associate and Brendan Harley, Associate Professor of Chemical and Biomolecular Engineering. Photo by L. Brian Stauffer, U of I News Bureau.
Postdoctoral research associate Ji Sun Choi and Associate Professor of Chemical and Biomolecular Engineering Brendan Harley. Credit: Photo by L. Brian Stauffer.

Researchers at the University of Illinois report they can alter blood cell development through the use of biomaterials designed to mimic characteristics of the bone marrow.

The findings, reported in the journal Science Advances, are a first step toward developing more effective bone marrow treatments for diseases like leukemia and lymphoma.

Blood cells flow throughout the body delivering life-supporting oxygen and nutrients. As these cells are used and recycled they are regenerated by bone marrow, the soft tissue inside the body’s long and hollow bones.

Certain regions of bone marrow contain hematopoietic stem cells, the precursors of all blood and immune cells, said University of Illinois chemical and biomolecular engineering professor Brendan Harley, who led the research with postdoctoral researcher Ji Sun Choi.

“The tissue environment that surrounds these cells in the bone marrow provides a wealth of signals that can alter how these precursor cells behave. This paper looked at the signals provided by the tissue matrix itself,” said Harley, who also is affiliated with the Carl R. Woese Institute for Genomic Biology at the U. of I.

One of the major tools that oncologists use to treat leukemia and lymphoma involves transplanting HSCs. The donor stem cells must locate marrow cavities and start producing blood and immune cells. However, there is a limited quantity of available donor HSCs and the success rate of transplantation is low.

“We’re interested in this problem from an engineering standpoint,” Harley said. “The goal is to create better tools to both expand the number of donor HSCs and improve their capacity to repopulate the bone marrow after transplantation.”

Like cells throughout the body, HSCs are contained in a three-dimensional tissue environment known as the extracellular matrix. Harley and Choi gathered samples of HSCs from mice and then grew them in the laboratory using biomaterials engineered to mimic some of the extracellular matrix properties of the native bone marrow. Their goal was to examine how these engineered systems could alter the HSCs’ capacity to proliferate and differentiate to become blood cells.

The researchers examined two main elements of the matrix that regularly interact with HSCs: collagen and fibronectin. They found that the HSCs that were exposed to collagen proliferated more rapidly but that they had differentiated, meaning they were no longer stem cells. When exposed to fibronectin, the stem cells proliferated less rapidly, but were able to maintain their stem cell-like nature.

“With the collagen substrates, we got more cells but not useful cells,” Harley said. “With the right combination of stiffness in the matrix and the presence of fibronectin, we identified a class of biomaterials that show promise for being able to maintain and eventually expand these stem cells outside of the body. An engineered bone marrow will be of enormous value for treating hematopoietic cancers such as leukemia, but also for understanding the process of bone marrow failure and other hematopoietic diseases.”

This project is only the first step in controlling the signals from the matrix that influence HSCs, Harley said. He and other researchers in his lab are currently investigating other features of the matrix that can be manipulated to increase the number of stem cells and make them more effective in transplantation.

The National Science Foundation, National Institutes of Health and the American Cancer Society of Illinois supported this research.

Editor’s notes:

by Sarah Banducci, University of Illinois News Bureau Intern

To reach Brendan Harley, call 217-244-7112; email bharley@illinois.edu.

The paper “Marrow-inspired matrix cues rapidly affect early fate decisions of hematopoietic stem and progenitor cells” is available online and from the News Bureau. DOI: 10.1126/sciadv.1600455

Brendan Harley, Associate Professor in the Department of Chemical and Biomolecular Engineering, has received a two-year grant from the National Science Foundation for “EAGER: Biomanufacturing the hematopoietic stem cell niche.”

Associate Professor Brendan A. Harley
Associate Professor Brendan A. Harley

Working with Professor Bruce Hannon of the University of Illinois Department of Geography and Geographic Information Science, the project will demonstrate approaches that integrate traditional experimental tools with rules-based models in order to design a stem cell biomanufacturing platform to selectively expand donor hematopoietic stem cells.

The effort will use tools previously developed to study ecological and economic sustainability in fishery and other wildlife population management questions to examine the dynamics of stem cells.

The project’s objective is to demonstrate a new paradigm for advanced stem cell manufacturing. Hematopoiesis is the process where the body’s blood and immune cells are generated from a small number of hematopoietic stem cells (HSCs) whose behavior is regulated by regions of the bone marrow termed niches. There is an unmet clinical need for stem cell biomanufacturing approaches to selectively expanding donor HSCs while also priming them for HSC transplants used to treat a wide range of hematologic diseases.

Learn more about the announcement from the NSF.

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