Using a magnetic field and hydrogels, a team of researchers in the Perelman School of Medicine have demonstrated a new possible way to rebuild complex body tissues, which could result in more lasting fixes to common injuries, such as cartilage degeneration. This research was published in Advanced Materials.
“We found that we were able to arrange objects, such as cells, in ways that could generate new, complex tissues without having to alter the cells themselves,” says the study’s first author, Hannah Zlotnick, a graduate student in bioengineering who works in the McKay Orthopaedic Research Laboratory at Penn Medicine. “Others have had to add magnetic particles to the cells so that they respond to a magnetic field, but that approach can have unwanted long-term effects on cell health. Instead, we manipulated the magnetic character of the environment surrounding the cells, allowing us to arrange the objects with magnets.”
In humans, tissues like cartilage can often break down, causing joint instability or pain. Often, the breakdown isn’t in total, but covers an area, forming a hole. Current fixes are to fill those holes in with synthetic or biologic materials, which can work but often wear away because they are not the same exact material as what was there before. It’s similar to fixing a pothole in a road by filling it with gravel and making a tar patch: The hole will be smoothed out but eventually wear away with use because it’s not the same material and can’t bond the same way.
What complicates fixing cartilage or other similar tissues is that their makeup is complex.
“There is a natural gradient from the top of cartilage to the bottom, where it contacts the bone,” Zlotnick explains. “Superficially, or at the surface, cartilage has a high cellularity, meaning there is a higher number of cells. But where cartilage attaches to the bone, deeper inside, its cellularity is low.”
So the researchers, which included senior author Robert Mauck, PhD, director of the McKay Lab and a professor of Orthopaedic Surgery and Bioengineering, sought to find a way to fix the potholes by repaving them instead of filling them in. With that in mind, the research team found that if they added a magnetic liquid to a three-dimensional hydrogel solution, cells, and other non-magnetic objects including drug delivery microcapsules, could be arranged into specific patterns that mimicked natural tissue through the use of an external magnetic field.
Drugs are commonly injected directly into an injury site to speed healing. For chronic pain, clinicians can inject drugs to reduce inflammation in painful joints, or can inject nerve blockers to block the nerve signals that cause pain. In a recent study, a group from UCLA developed a technique to deform a material surrounding nerve fibers to trigger a response in the fibers that would relieve pain. The combination of mechanics and treatment – i.e., ‘mechanoceuticals’ – is a clever way to trick fibers and reverse painful symptoms. Done without any injections and simply controlling magnetic fields outside the body, this approach can be reused as necessary.
The design of this mechanoceutical was completed by Dino Di Carlo, PhD, Professor of Bioengineering, and his team at UCLA’s Sameuli School of Engineering. By encasing tiny, magnetic nanoparticles within a biocompatible hydrogel, the group used magnetic force to stimulate nerve fibers and cause a corresponding decrease in pain signals. This promising development opens up a new approach to pain management, one which can be created with different biomaterials to suit different conditions, and delivered “on demand” without worrying about injections or, for that matter, any prescription drugs.
Understanding the Adolescent Brain
It’s no surprise that adults and adolescents often struggle to understand one another, but the work of neurologists and other researchers provides a possible physical reason for why that might be. Magnetic resonance elastrography (MRE) is a tool used in biomedical imaging to estimate the mechanical properties, or stiffness, of tissue throughout the body. Unexpectedly, a recent study suggests that brain stiffness correlates with cognitive ability, suggesting MRE may provide insight into patients’ behavior, psychology, and psychiatric state.
A new paper in Developmental Cognitive Neuroscience published the results of a study using MRE to track the relative “stiffness” vs. “softness” of adult and adolescent brains. The University of Delaware team, led by Biomedical Engineering Assistant Professor Curtis Johnson, PhD, and his doctoral student Grace McIlvain, sampled 40 living subjects (aged 12-14) and compared the properties to healthy adult brains.
The study found that children and adolescent brains are softer than those of adults, correlating to the overall malleability of childhood development. The team hopes to continue their studies with younger and older children, looking to demonstrate exactly when and how the change from softness to stiffness takes place, and how these properties correspond to individual qualities such as risk-taking or the onset of puberty. Eventually, establishing a larger database of measurements in the pediatric brain will help further studies into neurological and cognitive disorders in children, helping to understand conditions such as multiple sclerosis, autism, and cerebral palsy.
Can Nanoparticles Replace Stents?
Researchers and clinicians have made amazing advances in heart surgery. Stents, in particular, have become quite sophisticated: they are used to both prop open clogged arteries as well as deliver blood-thinning medication slowly over days to weeks in the area of the stent. However, the risk of blood clotting increases with stents and the blood vessels can constrict over time after the stent is placed in the vessel.
A recent NIH grant will support the design of a stent-free solution to unclog blood vessels. Led by Shaoqin Gong, PhD, Vilas Distinguished Professor of Biomedical Engineering at UW-Madison, the team used nanoparticles (or nanoclusters) to directly target the affected blood vessels and prevent regrowth of the cells post-surgery, eliminating the need for a stent to keep the pathways open. These nanoclusters are injected through an intravenous line, further reducing the risks introduced by the presence of the stent. As heart disease affects millions of people worldwide, this new material has far-reaching consequences. Their study is published in the September edition of Biomaterials.
NIST Grant Supports
The National Institute of Standards and Technology (NIST) awarded a $30 million grant to Johns Hopkins University, Binghamton University, and Morgan State University as part of their Professional Research Experience Program (PREP). Over five years, this award will support the collaboration of academics from all levels (faculty, postdoc, graduate, and undergraduate) across the three universities, enabling them to conduct research and attend NIST conferences.
The principal investigator for Binghamton U. is Professor and Chair of the Biomedical Engineering Department, Kaiming Ye, PhD. Dr. Ye is also the Director of the Center of Biomanufacturing for Regenerative Medicine (CBRM), which will participate in this collaborative new enterprise. Dr. Ye hopes that this grant will create opportunities for academics and researchers to network with each other as well as to more precisely define the standards for the fields of regenerative medicine and biomaterial manufacturing.
The gift honors the late A. James Clark, former CEO of Clark Enterprises and Clark Construction Group LLC, one of the country’s largest privately-held general building contractors. It is designed to prepare future engineering and business leaders, with an emphasis on low income families and first-generation college students. Clark never forgot that his business successes began with an engineering scholarship. This has guided the Clark family’s longstanding investments in engineering education and reflects its commitment to ensure college remains accessible and affordable to high-potential students with financial need.
We are proud to say that three incoming Clark Scholars from the Freshman Class of 2022 will be part of the Bioengineering Department here at Penn.
And finally, our congratulations to the new Dean of the School of Engineering at the University of Mississippi: David A. Puleo, PhD. Dr. Puleo earned his bachelor’s degree and doctorate in Biomedical Engineering from Rensselaer Polytechnic Institute. Most recently he served as Professor of Biomedical Engineering and Associate Dean for Research and Graduate Studies at the University of Kentucky’s College of Engineering. Building on his research in regenerative biomaterials, he also founded Regenera Materials, LLC in 2014. Over the course of his career so far, Dr. Puleo received multiple teaching awards and oversaw much departmental growth within his previous institution, and looks poised to do the same for “Ole Miss.”