Researchers in Beckman’s Autonomous Materials Systems Group created “growth printing,” which mimics tree trunks’ outward expansion to print polymer parts quickly and efficiently without the molds and expensive equipment typically associated with 3D printing. Their work appears in the journal Advanced Materials.

“Humans are incredibly talented at making things. Completely new manufacturing processes are hard to find. Growth printing is entirely new, which is thrilling,” said Sameh Tawfick , a professor of mechanical science and engineering at the University of Illinois Urbana-Champaign and project lead.

Tawfick said the most common industrial manufacturing technology is injection molding, where molten polymers take shape in a metal mold. Though effective for mass production, maintaining the molds and curing ovens (where the plastic hardens) can be cost-prohibitive and unwieldy — especially for large objects like boat hulls or fan blades. Additive manufacturing, which prints 3D objects like a layer cake, is mold-less and ideal for custom parts like prosthetics.

“Polymer 3D printing equipment has matured, but there are still aspects that make it expensive and very slow,” Tawfick said. “Our goal was to increase the manufacturing speed, size and material quality while maintaining a low cost. This process that we came up with is truly fast and inexpensive.”

First, Sameh and his colleagues pour amber-colored liquid resin called dicyclopentadiene, or DCPD, into an open glass container submerged in ice water. They heat a center point in the resin to 70C. As the reaction takes over, heat radiates outward from the original point of contact at 1 mm/s, more than 100 times faster than the desktop 3D printers available for home use and 60 times faster than the world’s fastest-growing species of bamboo. Everything the heat touches hardens into a growing sphere, like if the mythical King Midas seized the Earth’s core. Self-sustained by heat’s steady release, the reaction — called frontal ring-opening metathesis polymerization and nicknamed FROMP — uses minimal energy to harden the resin into its solid form: poly- dicyclopentadiene, or p-DCPD.

As the hardened sphere grows, the researchers alter its shape by pulling it out of the resin like an apple out of gooey caramel. Since the liquid-to-solid reaction only happens below the surface, the researchers can lift, dip or spin the solid part like blown glass to manipulate its size and shape. For example: to create a corrugated, or wavy, edge, the researchers lift the resin slightly, hold it still, and repeat.

The researchers designed their process to mimic how a tree steadily expands outward, ring by ring. In nature, elements like gravity, wind and temperature complement and complicate a tree’s tendency to grow symmetrically, resulting in trees that bow in the wind or reach toward a patch of sunlight in the forest canopy.

Tawfick became enamored of living organisms’ growth patterns and resulting shapes — also known as morphogenesis — upon reading D’Arcy Wentworth Thompson’s book, “On Growth and Form.” Last August, when Tawfick was promoted from associate professor to full professor, he dedicated the book to the University Library.

Using their new method, Tawfick and his colleagues fabricated everyday items such as a pinecone, a raspberry and a squash. These are all axisymmetrical shapes, or symmetrical around a vertical axis. Non-symmetrical shapes are more difficult, but possible; for example, the researchers sculpted a kiwi bird by allowing the spherical body to expand below the surface before pulling it up just in time to create a diminutive head and minute beak.

“It is a beautiful and simple application of a reaction-diffusion process, which is found in many natural systems. The speed and energy efficiency of the growth-printing process make this process particularly attractive. On the modeling side of this collaborative project, we developed a computational tool that predicts the upward motion of the rod needed to achieve a target shape of the manufactured object,” said Philippe Geubelle, Illinois professor of aerospace engineering and co-author on the paper.

This method’s limitations are the same ones found in nature. Printing curved objects, like bananas, is theoretically possible but difficult to program mathematically, as are complex shapes “like a thorn in a rose,” Tawfick said.

“It’s hard to find a perfect cube in nature. I don’t know of any plant or organism that looks like a perfect cube. Similarly, our process cannot make a perfect cube. It’s an interesting mirror of nature,” he said.

Tawfick says the process is “simple and highly marketable” and hopes it can one day be used to create large polymer-based products like wind turbine blades. The project is funded through the U.S. Department of Energy Office of Science Basic Energy Sciences program.

“Basic energy science could lead to transformative manufacturing, meaning something with a transformative impact on our economy. This is a successful example and was made possible through collaboration here at the Beckman Institute with people from all areas of expertise,” Tawfick said.

First author and Illinois graduate student Yun Seong Kim said the project demonstrated true teamwork:

“It was really a work of true teamwork, because it required expertise in various backgrounds and we all came together to make it happen,” he said.

Coauthor Randy Ewoldt, the Alexander Rankin Professor of Mechanical Science and Engineering at Illinois, adds: “The many advances of this work resulted because of the outstanding teamwork. The Illinois culture of collaborative excellence shines bright.”

Scientists have long studied the ins and outs of cancer cells to learn more about the disease, but they’re increasingly finding that noncancerous cells near the cancer cells exert a powerful influence over a tumor’s trajectory.

“Not all cells in a tumor are cancer cells — they’re not even always the most dominant cell type,” said Sylvia Plevritis, PhD, chair of Stanford Medicine’s department of biomedical data science. “There are many other cell types that support tumors.”

To better capture the whole picture of cells’ locations and interactions, Plevritis and a team of researchers have developed something that they call the “colocatome,” (pronounced co-locate-ome). Modeled after the nomenclature that describes other classes of molecules and facets of human biology (collective information about genes is called the genome; proteins, the proteome; metabolites, the metabolome, etc.) the colocatome documents the details of malignant cells on their neighbors — what those cells are and how many of them are present.

“We’ve been studying cancer cells for so long, but the picture is still incomplete,” said Gina Bouchard, PhD, instructor of biomedical data science. “Understanding tumor biology is not only about cancer cells; there’s a whole ecosystem that needs to be studied. Cancer cells need help to survive, to resist, to thrive and even sometimes to die.”

A study describing the findings was published in Nature Communications last month. Bouchard is the lead author, and Plevritis is the senior author.

Mapping influence

Cancer cells are surprisingly dependent on their surroundings. Depending on the location, type and quantity of noncancerous cells surrounding the tumor, the cells’ behavior can change, whether through faster growth, decreased susceptibility to drugs or heightened cell metabolism.

“The questions we’re asking are very simple. We want to know who the neighbors are for each cell. Who likes whom? Who doesn’t like whom? It’s all about which cells tend to be together, and which ones are rarely found together,” Bouchard said. Cells that attract each other are described as “colocalizing” while those that seem to repel each other form “anti-colocalizations.” Those colocalizations are then linked to the state of the cancer — aggressive, resistant, susceptible to drugs — and logged in the colocatome.

The team developed experimental models of lung cancer in the lab, then used artificial intelligence to analyze them, identifying noncancerous cells and how they organized within and around the tumor cells. They then compared the colocalizations with those from patient tumor biopsies. After mapping hundreds of cell configurations, they confirmed that the majority of colocalizations in the primary patient tumors are observed in the experimental models. (That overlap is key, said Bouchard. It means that the models are a valuable and accurate representation of what’s happening in someone who has lung cancer.)

Past research by Plevritis and others showed strong interactions between fibroblasts and cancer cells, but exactly how fibroblasts interact with cancer cells is unclear. In an experiment, Plevritis showed that lung cancer cells die when doused with a type of anti-tumor drug that stunts cell growth. But throw fibroblasts into the mix, and the entire landscape changes — literally. Plevritis mapped the treated tumor models and saw that post-treatment, the cancer cells and fibroblasts were generally left intact in the same amount. But they had rearranged themselves.

“That spatial reorganization appears to have given rise to drug-resistance,” said Plevritis, the William M. Hume Professor in the School of Medicine. “It was like changing the furniture in the room, then finding the exits are blocked.”

Chasing new leads

As the team continues to log spatial maps of treated and untreated tumors, they hope to unlock more configurations that help clue doctors in on why some cancers persist after treatment. Ideally, the researchers said, the colocatome could provide information that guides treatment of patient’s cancer: If a specific colocalization confers resistance to a common drug, for instance, physicians can search for another that might have a better chance of working. They also hope the colocalization maps will generate testable hypotheses to describe aspects of cancer biology that remain unclear.

As they collect more data, the team plans to employ AI to identify specific spatial motifs and create catalogs of maps that correspond to different cell states for a variety of cancers. “Then we can begin to see whether certain spatial motifs are shared between cancer types, regardless of where they originate in the body. That could reveal universal rules of tumor behavior and guide the design of more broadly effective treatments,” Plevritis said. “That’s something I’m really excited about.”

A researcher from the University of Oxford contributed to this research.

This study was funded by the National Institute of Health (grants R25CA180993, U54CA274511 and K99CA255586) and Les Fonds de Recherche du Québec.

Stanford’s Department of Biomedical Data Sciences also supported the work.

In clinical settings, IV infusions are packaged in individual plastic pouches and deliver water, electrolytes, nutrients or medicine to patients. The base of these infusions is a saline solution that contains filtered water and enough salt to match the content of human blood. Research from the 1970s suggests IV fluid bags can contain solid particles, but few scientists have followed up on what those particles are made of. Liwu Zhang, Ventsislav Kolev Valev and colleagues suspected that these particles could be microplastics that, upon infusion, would enter the recipient’s bloodstream and potentially cause negative health effects. So, they set out to analyze the types and amounts of particles in commercial IV fluid bags.

The team purchased two different brands of 8.4-ounce bags of IV saline solution. After the contents of each bag dripped into separate glass containers, the liquids were filtered to catch microscopic particles. Then the researchers counted a portion of the individual plastic fragments, using that amount to estimate the total number of microplastics in the entire pouch of IV liquid and to analyze the composition of the particles.

The researchers discovered that both brands of saline contained microplastic particles made from polypropylene — the same material as the bags — which suggests that the bags shed microplastics into the solutions. And they estimated that each bag of infusion fluid could deliver about 7,500 microplastics directly into the bloodstream. This figure rises to about 25,000 particles to treat dehydration or 52,500 for abdominal surgery, which can require multiple IV bags.

The researchers recommend keeping IV infusion bags away from ultraviolet light and heat to reduce microplastic shedding, and they say that micrometer-level filtration systems could be used to remove the particles during infusion.

While there are no clinical studies to date that have assessed the health risks of microplastics exposure, the researchers say their findings will help “provide a scientific basis for formulating appropriate policies and measures to mitigate the potential threats posed by microplastics to human health.”

The authors acknowledge funding from the National Natural Science Foundation of China.