By manipulating the physical characteristics of matter at its smallest sizes, researchers can create materials that are stronger, more flexible, and more durable at the macro scale. We look at two labs doing just that: one creating biomaterials for stem cell transplants and tissue regeneration, and the second manufacturing customized medical devices and implants for newborns.July 10, 2017
In their struggle to keep premature newborns alive, physicians depend on catheters to infuse medications and nutrients into their patients. Unfortunately, preemies differ from one another in size, shape, and location of veins and organs. Off-the-shelf neonatal catheters may not reach a critical spot, or may puncture a vein because they fail to accommodate an unusual physiological feature.
Randall Erb, professor of mechanical and industrial engineering at Northeastern University, hopes to overcome those problems by using 3D printing to create customized reinforced catheters.
Reinforcement is important because neonatal catheters are much smaller and thinner than adult catheters, so they break easily. Erb’s advance involves using magnets to orient ceramic reinforcements around catheter curves and holes to strengthen them. The result is a delicate catheter with surprising durability.
“Traditional 3D printing has enabled the creation of materials with complex and programmable geometries,” says Erb. “However, making complex geometries out of ceramic-reinforced composite materials is a challenge, since local control over the ceramic elements is required to increase strength and toughness.”
Erb hurdles that challenge by coating alumina or glass, two common ceramic reinforcements, with small amounts (usually less than 0.1 percent by weight) of iron oxide. This is enough to enable the magnets to grab the fibers. Erb then steers them to form reinforcement architectures that strengthen the complex geometries of the printed parts.
“In a printed structure, we can now control the ceramic fiber orientation in every single 50 micrometer voxel of space,” sys Erb, referring to the 3D grid created by CAD programs. “This allows us to produce composites with the highest resolution and control of reinforcement architecture to date.”
To do this, Erb’s team modified an open-source stereolithographic printer by adding large electromagnetic solenoids to the frame. They then rewrote the control code to apply magnetic fields autonomously during printing. The new code enables the system to orient the reinforcements in different directions while printing a single layer.
“Although this slows down the print, a 5 x 5 inch sample takes only 30 seconds per layer to texture and print, depending on the design complexity of the ceramic reinforcement architecture,” Erb said.
Erb’s team is now investigating new ways to apply the technology to custom products. He has received a $225,000 Small Business Technology Transfer grant from the National Institutes of Health to develop neonatal catheters with a local company. He is also looking into printing soldier-specific armor and helmets.
Creating Bone Cells
Our cells contain all our genetic information, but our interactions with our environment determine which of our genes are active, or expressed, at any given time. By engineering new types of matrices to house and support cells, Harvard University’s Laboratory for Cell and Tissue Engineering seeks to create environments that promote the regeneration or targeted destruction of tissues and organs in the body.
Lab director David Mooney’s team, including post-doctoral fellows Ovi Chaudhuri and Luo Gu, has developed a better way to encourage stem cells to develop into bone cells. Surprisingly, it involves adjusting the mechanical properties of matrix surrounding the cells.
The researchers started by testing the stiffness of the bone cell microenvironment. Ordinarily, it is viscoelastic: like chewing gum, it relaxes with stress and dissipates energy over time when a strain is applied.
Mooney’s team then synthesized hydrogels with different stress relaxation responses to mimic the viscoelasticity of different bone microenvironments, and placed stem cells into them. The more viscous and less elastic the matrix, the more likely the stem cells developed into bone cells and formed bone-like material.
Controlling matrix viscoelasticity enables the team to exploit and control stem cell behaviors, says Chaudhuri. Yet to achieve precise control, the team needed to tease out how stress relaxation affects stem cells independently from stiffness.
That meant synthesizing a molecule where those two properties were not dependent on one another. They started with alginates, sugars naturally derived from algae. The higher the molecular weight of the sugar, that is, the bigger the sugar’s molecular building blocks, the stiffer the matrix it formed. Then they added side chains to the molecules.
“This interferes with the packing of individual polymer chains, making it easier for them to move relative to each other and thus altering the rate of stress relaxation,” says Gu.
The research team is currently testing some of the biomaterials in animals for bone regeneration.
It turns out that matrix viscoelasticity and stress relaxation play a significant role in many biological processes. Mooney’s team hopes to exploit this type of regulation to design biomaterials for stem cell transplantation and regenerative medicine.
“We hope this discovery highlights the importance of matrix stress relaxation in directing cell fate and activities,” says Mooney. “Perhaps in the future stress relaxation will be used as a design parameter for regenerating or engineering bone, as well as an array of other tissue types.
Mark Crawford is an independent technical writer from Wisconsin.