Bioengineering: In-Depth Description

Bioengineering is an interdisciplinary field that applies engineering principles, design concepts, and quantitative methods to biological systems. It bridges the gap between engineering and the life sciences to create solutions for problems in biology, medicine, agriculture, and environmental science. Its primary goals are to analyze and understand complex biological systems and to develop new technologies, materials, and therapies to improve human health, quality of life, and sustainability.

New ultrasound technique could help aging and injured brains

Raag Airan, Matine Azadian, Payton Martinez, and Yun Xiang in the lab. Azadian is holding a version of their ultrasound apparatus designed for humans.
Photo Credit: Andrew Brodhead

Just like your body needs a bath now and then, so too does your brain – but instead of a tub filled with hot water, your brain has cerebrospinal fluid, which flows around inside the brain and helps clear away waste products, misplaced blood cells, and other sometimes-toxic debris.

The trouble is, that natural brain-bathing system can break down as people age or after a brain injury, such as a stroke – and there aren’t any particularly good ways to help the brain out in those situations. Indeed, current ideas to promote cerebrospinal fluid cleaning are either rather invasive or require drugs that may not be safe or effective in people.

Fortunately, a team of Stanford researchers has found a radically simple tool that may help the brain wash itself out without the need for drugs or invasive procedures: ultrasound, the same tool obstetricians regularly use at prenatal checkups.

Nonsurgical treatment shows promise for targeted seizure control

Jerzy Szablowski
Photo Credit: Jeff Fitlow/Rice University

Rice University bioengineers have demonstrated a nonsurgical way to quiet a seizure-relevant brain circuit in an animal model. The team used low-intensity focused ultrasound to briefly open the blood-brain barrier (BBB) in the hippocampus, delivered an engineered gene therapy only to that region and later flipped an on-demand “dimmer switch” with an oral drug. The research shows that a one-time, targeted procedure can modulate a specific brain region without impacting off-target areas of the brain.

“Many neurological diseases are driven by hyperactive cells at a particular location in the brain,” said study lead Jerzy Szablowski, assistant professor of bioengineering and a member of the Rice Neuroengineering Initiative. “Our approach aims the therapy where it is needed and lets you control it when you need it, without surgery and without a permanent implant.”

Nanorobots transform stem cells into bone cells

Prof. Berna Özkale Edelmann, together with researchers at her Microrobotic Bioengineering Lab at the Technical University of Munich (TUM), developed a system in which stem cells can be transformed into bone cells through mechanical stimulation.
Photo Credit: Astrid Eckert / Technische Universität München

For the first time, researchers at the Technical University of Munich (TUM) have succeeded in using nanorobots to stimulate stem cells with such precision that they are reliably transformed into bone cells. To achieve this, the robots exert external pressure on specific points in the cell wall. The new method offers opportunities for faster treatments in the future.

Prof. Berna Özkale Edelmann’s nanorobots consist of tiny gold rods and plastic chains. Several million of them are contained in a gel cushion measuring just 60 micrometers, together with a few human stem cells. Powered and controlled by laser light, the robots, which look like tiny balls, mechanically stimulate the cells by exerting pressure. “We heat the gel locally and use our system to precisely determine the forces with which the nanorobots press on the cell – thereby stimulating it,” explains the professor of nano- and microrobotics at TUM. This mechanical stimulation triggers biochemical processes in the cell. Ion channels change their properties, and proteins are activated, including one that is particularly important for bone formation.

SwRI-developed bioreactor replicates versatile induced Pluripotent Stem Cells

Southwest Research Institute demonstrated its single-use 3D bioreactor to produce induced Pluripotent Stem Cells (iPSCs), derived from adult skin, blood, and other somatic cells. Useful for personalized medicine, iPSCs offer an alternative to embryonic stem cells by differentiating into any other cell type in the body.
Photo Credit: Southwest Research Institute

Southwest Research Institute (SwRI) has demonstrated a new application for its cell-expansion bioreactor to advance tissue engineering and cell-based therapies for treatment of injuries and diseases. 

SwRI scientists used the bioreactor to replicate induced Pluripotent Stem Cells (iPSCs) derived from adult skin, blood, and other somatic cells. Their pluripotent state allows iPSCs to differentiate into any other cell type in the body, much like embryonic stem cells but without the same ethical ambiguity. Large quantities of iPSCs are needed for regenerative medicine and individualized healthcare, but current technology requires manual production. 

Prime time for fiber optics to take a deep dive into brain circuits

Fiber-optic technology is being refined for brain research. WashU engineers have developed a way to vastly expand the utility of a single fiber-optic line that can fit in the brain.
Image Credit: JJ Ying

Fiber-optic technology revolutionized the telecommunications industry and may soon do the same for brain research.

A group of researchers from Washington University in St. Louis in both the McKelvey School of Engineering and the School of Medicine have created a new kind of fiber-optic device to manipulate neural activity deep in the brain. The device, called PRIME (Panoramically Reconfigurable IlluMinativE) fiber, delivers multi-site, reconfigurable optical stimulation through a single, hair-thin implant.

“By combining fiber-based techniques with optogenetics, we can achieve deep-brain stimulation at unprecedented scale,” said Song Hu, professor of biomedical engineering, who collaborated with the laboratory of Adam Kepecs, professor of neuroscience and psychiatry at WashU Medicine. 

Controlling prostheses with the power of thought

 A neuroprosthesis. Artificial hands, arms, or legs can restore mobility to people with disabilities. The study investigated how the brain learns to control such prostheses via brain-computer interfaces.
Image Credit: © Sebastian Lehmann

Researchers at the German Primate Center (DPZ) – Leibniz Institute for Primate Research in Göttingen have discovered that the brain reorganizes itself extensively across several brain regions when it learns to perform movements in a virtual environment with the help of a brain-computer interface. The scientists were thus able to show how the brain adapts when controlling motor prostheses. The findings not only help to advance the development of brain-computer interfaces, but also improve our understanding of the fundamental neural processes underlying motor learning.

In order to perform precise movements, our brain's motor system must continuously recalibrate itself. If we want to shoot a basketball, this works well with a familiar basketball, but requires extra practice with a lighter or heavier ball. Our brain uses the deviations from the expected (throw) result as an error signal to learn better commands for the next throw. The brain must also perform this task when it wants to control a movement via a brain-computer interface (BCI), for example, that of a neuroprosthesis. Until now, it was unclear which regions of the brain reflect the expected result of the movement (the trajectory of the ball), which reflect the error signal, and which reflect the corrected movement command that aims to compensate for the previous error.

In a surprising discovery, scientists find tiny loops in the genomes of dividing cells

MIT experiments have revealed the existence of “microcompartments,” shown in yellow, within the 3D structure of the genome. These compartments are formed by tiny loops that may play a role in gene regulation.
Illustration Credit: Ed Banigan, edited by MIT News
(CC BY-NC-ND 4.0)

Before cells can divide, they first need to replicate all of their chromosomes, so that each of the daughter cells can receive a full set of genetic material. Until now, scientists had believed that as division occurs, the genome loses the distinctive 3D internal structure that it typically forms.

Once division is complete, it was thought, the genome gradually regains that complex, globular structure, which plays an essential role in controlling which genes are turned on in a given cell.

However, a new study from MIT shows that in fact, this picture is not fully accurate. Using a higher-resolution genome mapping technique, the research team discovered that small 3D loops connecting regulatory elements and genes persist in the genome during cell division, or mitosis.

“This study really helps to clarify how we should think about mitosis. In the past, mitosis was thought of as a blank slate, with no transcription and no structure related to gene activity. And we now know that that’s not quite the case,” says Anders Sejr Hansen, an associate professor of biological engineering at MIT. “What we see is that there’s always structure. It never goes away.”

Researchers use nanotubes to improve blood flow in bioengineered tissues

Assistant Professors Ying Wang (Department of Biomedical Engineering) and Yingge Zhou (School of Systems Science and Industrial Engineering) collaborated on research about engineered tissues.
Photo Credit: Jonathan Cohen.

When biomedical researchers need to test their latest ideas, they often turn to engineered human tissue that mimics the responses in our own bodies. It’s become an important intermediary step before human clinical trials.

One limiting factor: The cells need blood circulation to survive, and achieving that can be difficult in three-dimensional cell structures. Without proper vascular systems — even primitive ones — engineered tissue faces restricted size and functionality, even developing necrotic regions of dead cells.

New research from Binghamton University’s Thomas J. Watson College of Engineering and Applied Science offers a possible solution to the problem. In a paper recently published in the journal Biomedical Materials, Assistant Professors Ying Wang and Yingge Zhou show how the latest nanomanufacturing techniques can create a better artificial vascular system.

Brain inflammation treatment could be ally in fight against dementia

Samira Aghlara-Fotovat
Photo Credit: Jeff Fitlow/Rice University

Scientists from Rice University and Houston Methodist have developed a new way to reduce inflammation in the brain, a discovery that could help fight diseases such as Alzheimer’s and Parkinson’s.

The team created “AstroCapsules,” small hydrogel capsules that enclose human astrocytes ⎯ star-shaped brain cells that support healthy nervous system function. Inside the capsules, the cells were engineered to release interleukin-1 receptor antagonist, an anti-inflammatory protein. Tests in human brain organoids and mouse models showed the treatment lowered neuroinflammation and resisted immune rejection.

Rice bioengineer Omid Veiseh, whose lab studies how to design biomaterials that work with the immune system, is co-corresponding author on the paper published in Biomaterials.

“Encapsulating cells in a way that shields them from immune attack has been a central challenge in the field,” said Veiseh, professor of bioengineering at Rice, Cancer Prevention and Research Institute of Texas Scholar and director of the Rice Biotech Launch Pad. “In our lab, we have been working on biomaterials for many years, and this project was an opportunity to draw from that experience to address the uniquely complex immune environment of the brain. Our hope is that this work will help move cell therapies closer to becoming real treatment options for patients with neurodegenerative disease.”

Lung-on-a-Chip Defends Itself

Ankur Singh and Rachel Ringquist point to the microscopic lung-on-a-chip that has a built-in immune system.
Photo Credit: Courtesy of Georgia Institute of Technology

On a clear polymer chip, soft and pliable like a gummy bear, a microscopic lung comes alive — expanding, circulating, and, for the first time, protecting itself like a living organ. 

For Ankur Singh, director of Georgia Tech’s Center for Immunoengineering, watching immune cells rush through the chip took his breath away. Singh co-directed the study with longtime collaborator Krishnendu “Krish” Roy, former Regents Professor and director of the NSF Center for Cell Manufacturing Technologies at Tech and now the Bruce and Bridgitt Evans dean of engineering and University Distinguished Professor at Vanderbilt University. Rachel Ringquist, Roy’s graduate student, and now a postdoctoral fellow with Singh, led the work as part of her doctoral dissertation. 

“That was the ‘wow’ moment,” Singh said. “It was the first time we felt we had something close to a real human lung.”

Lung-on-a-chip platforms provide researchers a window into organ behavior. They are about the size of a postage stamp, etched with tiny channels and lined with living human cells. Roy and Singh’s innovation was adding a working immune system — the missing piece that turns a chip into a true model of how the lung fights disease.

Now, researchers can watch how lungs respond to threats, how inflammation spreads, and how healing begins.

Visualisation of blood flow sharpens artificial heart

To be able to observe the blood flow in the artificial heart in real time, the researchers had to build a full-scale model of the human circulatory system.
Photo Credit:Emma Busk Winquist

Using magnetic cameras, researchers at Linköping University have examined blood flow in an artificial heart in real time. The results make it possible to design the heart in a way to reduce the risk of blood clots and red blood cells breakdown, a common problem in today’s artificial hearts. The study, published in Scientific Reports, was done in collaboration with the company Scandinavian Real Heart AB, which is developing an artificial heart.

“The heart is a muscle that never rests. It can never rest. The heart can beat for a hundred years without being serviced or stopping even once. But constructing a pump that can function in the same way – that’s a challenge,” says Tino Ebbers, professor of physiology at Linköping University.

Nearly 9,000 heart transplants are performed worldwide per year, and the number keeps increasing. So does the number of people queuing for a new heart, with some 2,800 on the waiting list in the EU alone, and around 3,400 in the US.

Most of the patients whose heart does not work at all are currently connected to a machine that takes care of their blood circulation for them. It is a large device, and the patient is confined to their hospital bed. For those patients, an artificial heart could be an option while waiting for a donor heart.

New Diagnostic Tool Developed at Dana-Farber Revolutionizes Acute Leukemia Diagnosis

Volker Hovestadt, PhD
Assistant Professor, Pediatrics, Harvard Medical School Independent Investigator/Assistant Professor, Department of Pediatric Oncology, Dana-Farber Cancer Institute
Photo Credit: Courtesy of Dana-Farber Cancer Institute

Researchers at Dana-Farber Cancer Institute have developed a groundbreaking diagnostic tool that could transform the way acute leukemia is identified and treated. The tool, called MARLIN (Methylation- and AI-guided Rapid Leukemia Subtype Inference), uses DNA methylation patterns and machine learning to classify acute leukemia with speed and accuracy. This tool has the potential to significantly improve patient care by allowing faster and more precise treatment decisions.

Acute leukemia is an aggressive blood cancer that requires accurate diagnosis to guide treatment. Current diagnostic methods, which rely on a combination of molecular and cytogenetic tests, often take days or even weeks to complete. MARLIN, however, can provide results in as little as two hours from the time of biopsy. By providing rapid and detailed insights into leukemia subtypes, MARLIN could enable clinicians to make treatment decisions sooner and with more complete information.

Possible breakthrough in the development of effective biomaterials

Professor Dr. Shikha Dhiman from the Department of Chemistry of JGU
Photo Credit: © Ankit Sakhuja

When model cell membranes bind to biomaterials, it is not the binding strength but the speed of the receptors in the membranes that is crucial

Many hopes rested on so-called tissue engineering: With the help of stem cells, skin and other organs could be grown, thereby enabling better wound healing and better transplants. Although some of this is already a reality, the level expected around 20 years ago has not yet been achieved because the stem cells do not always bind to the required host material as they should in theory. An international research team led by chemist Professor Shikha Dhiman from Johannes Gutenberg University Mainz (JGU) has now found the reason for this: "Whether an interaction between model cell membrane and matrix material occurs depends not only on the strength of the interaction but also on the speed at which the binding partner molecules move. The understanding of this interaction that we have now gained is crucial for the development of effective biomaterials," says Dhiman. The team's results were recently published in the renowned scientific journal PNAS.

Shining a light on germs

Microbe hunters: Empa researchers Paula Bürgisser and Giacomo Reina from the Nanomaterials in Health laboratory in St. Gallen.
Photo Credit: Empa

Light on – bacteria dead. Disinfecting surfaces could be as simple as that. To turn this idea into a weapon against antibiotic-resistant germs, Empa researchers are developing a coating whose germicidal effect can be activated by infrared light. The plastic coating is also skin-friendly and environmentally friendly. A first application is currently being implemented for dentistry.

Antibiotic-resistant bacteria and emerging viruses are a rapidly increasing threat to the global healthcare system. Around 5 million deaths each year are linked to antibiotic-resistant germs, and more than 20 million people died during the COVID-19 virus pandemic. Empa researchers are therefore working on new, urgently needed strategies to combat such pathogens. One of the goals is to prevent the spread of resistant pathogens and novel viruses with smart materials and technologies.

Surfaces that come into constant contact with infectious agents, such as door handles in hospitals or equipment and infrastructure in operating theaters, are a particularly suitable area of application for such materials. An interdisciplinary team from three Empa laboratories, together with the Czech Palacký University in Olomouc, has now developed an environmentally friendly and biocompatible metal-free surface coating that reliably kills germs. The highlight: The effect can be reactivated again and again by exposing it to light.

Discovery of unexpected collagen structure could ‘reshape biomedical research’

Jeffrey Hartgerink is a professor of chemistry and bioengineering at Rice.
Photo Credit: Courtesy of Jeffrey Hartgerink / Rice University

Collagen, the body’s most abundant protein, has long been viewed as a predictable structural component of tissues. However, a new study led by Rice University’s Jeffrey Hartgerink and Tracy Yu, in collaboration with Mark Kreutzberger and Edward Egelman at the University of Virginia (UVA), challenges that notion, revealing an unexpected confirmation in collagen structure that could reshape biomedical research.

The researchers used advanced cryo-electron microscopy (cryo-EM) to determine the atomic structure of a packed collagen assembly that deviates from the traditionally accepted right-handed superhelical twist. Published in ACS Central Science, the study suggests collagen’s structural diversity may be greater than previously believed.

“This work fundamentally changes how we think about collagen,” said Hartgerink, professor of chemistry and bioengineering. “For decades, we have assumed that collagen triple helices always follow a strict structural paradigm. Our findings show that collagen assemblies can adopt a wider range of conformations than previously thought.”

WSU researcher pioneers new study model with clues to anti-aging

Jiyue Zhu and a student work in the laboratory.
Photo Credit: Courtesy of Washington State University

Washington State University scientists have created genetically-engineered mice that could help accelerate anti-aging research.

Globally, scientists are working to unlock the secrets of extending human lifespan at the cellular level, where aging occurs gradually due to the shortening of telomeres–the protective caps at the ends of chromosomes that function like shoelace tips to prevent unraveling. As telomeres shorten over time, cells lose their ability to divide for healthy growth, and some eventually begin to die.

But research studying these telomeres at the cellular level has been challenging in humans.

Now, a discovery by a WSU research team published today in the journal Nature Communications has opened the door to using genetically engineered mice.

Led by WSU College of Pharmacy and Pharmaceutical Sciences Professor Jiyue Zhu, the research team has developed mice that have human-like short telomeres, enabling the study of cellular aging as it occurs in the human body and within organs. Normally mice have telomeres that are up to 10 times longer than humans.

First-of-its-kind integrated dataset enables genes-to-ecosystems research

DOE national laboratory scientists led by Oak Ridge National Laboratory have developed the first tree dataset of its kind, bridging molecular information about the poplar tree microbiome to ecosystem-level processes.
Illustration Credit: Andy Sproles/ORNL, U.S. Dept. of Energy

The first-ever dataset bridging molecular information about the poplar tree microbiome to ecosystem-level processes has been released by a team of Department of Energy scientists led by Oak Ridge National Laboratory. The project aims to inform research regarding how natural systems function, their vulnerability to a changing climate, and ultimately how plants might be engineered for better performance as sources of bioenergy and natural carbon storage.

The data, described in Nature Publishing Group’s Scientific Data, provides in-depth information on 27 genetically distinct variants, or genotypes, of Populus trichocarpa, a poplar tree of interest as a bioenergy crop. The genotypes are among those that the ORNL-led Center for Bioenergy Innovation previously included in a genome-wide association study linking genetic variations to the trees’ physical traits. ORNL researchers collected leaf, soil and root samples from poplar fields in two regions of Oregon — one in a wetter area subject to flooding and the other drier and susceptible to drought. 

Details in the newly integrated dataset range from the trees’ genetic makeup and gene expression to the chemistry of the soil environment, analysis of the microbes that live on and around the trees and compounds the plants and microbes produce.

The dataset “is unprecedented in its size and scope,” said ORNL Corporate Fellow Mitchel Doktycz, section head for Bioimaging and Analytics and project co-lead. “It is of value in answering many different scientific questions.” By mining the data with machine learning and statistical approaches, scientists can better understand how the genetic makeup, physical traits and chemical diversity of Populus relate to processes such as cycling of soil nitrogen and carbon, he said. 

First atlas of the human ovary with cell-level resolution is a step toward artificial ovary

University of Michigan BME graduate student Jordan Machlin shows to prof. Ariella Shikanov and fellows grad student Margaret Brunette the images of oocytes in ovarian tissue she collected using RNA-fluorescence in situ hybridization.
Photo Credit: Marcin Szczepanski/Lead Multimedia Storyteller, Michigan Engineering

A new “atlas” of the human ovary provides insights that could lead to treatments restoring ovarian hormone production and the ability to have biologically related children, according to University of Michigan engineers.

This deeper understanding of the ovary means researchers could potentially create artificial ovaries in the lab using tissues that were stored and frozen before exposure to toxic medical treatments such as chemotherapy and radiation. Currently, surgeons can implant previously frozen ovarian tissue to temporarily restore hormone and egg production. However, this does not work for long because so few follicles—the structures that produce hormones and carry eggs—survive through reimplantation, the researchers say.

The new atlas reveals the factors that enable a follicle to mature, as most follicles wither away without releasing hormones or an egg. Using new tools that can identify what genes are being expressed at a single-cell level within a tissue, the team was able to home in on ovarian follicles that carry the immature precursors of eggs, known as oocytes.

Rapid, simultaneous detection of multiple bacteria achieved with handheld sensor

Marking bacteria electrochemically for rapid detection   
From left: Image of bacteria labeled with electrochemical markers, an electrochemical instrument to measure the data, and an image of the data displayed on a smartphone.     
Image Credit: Hiroshi Shiigi, Osaka Metropolitan University

Hearing the words E. coli or salmonella and food poisoning comes to mind. Rapid detection of such bacteria is crucial in preventing outbreaks of foodborne illness. While the usual practice is to take food samples to a laboratory to see the type and quantity of bacteria that forms in a petri dish over a span of days, an Osaka Metropolitan University research team has created a handheld device for quick on-site detection.

Led by Professor Hiroshi Shiigi of the Graduate School of Engineering, the team experimented with a biosensor that can simultaneously detect multiple disease-causing bacterial species within an hour.

“The palm-sized device for detection can be linked to a smartphone app to easily check bacterial contamination levels,” Professor Shiigi explained.

His team synthesized organic metallic nanohybrids of gold and copper that do not interfere with each other, so that electrochemical signals can be distinguished on the same screen-printed electrode chip of the biosensor. These organic−inorganic hybrids are made up of conductive polymers and metal nanoparticles. The antibody for the specific target bacteria was then introduced into these nanohybrids to serve as electrochemical labels.