Musculoskeletal tissue engineering focuses on the composition and function of things like menisci, tendons, ligaments, muscle and bone, which aid movement while providing joint support and stability. Biomedical engineering Ph.D. student Kelly Ott started her academic career as an undergraduate at the VCU College of Engineering and chose to continue her graduate studies at VCU, researching how mechanical cues can increase the organization of collagen structures.
“Being part of a well-established lab and familiarity with the biomedical engineering graduate program at VCU Engineering is a big reason for why I chose to continue at VCU,” Ott said. “Access to VCU resources like the Nanomaterials Core Characterization Facility (NCC) and Massey Cancer Center’s Tissue and Data Acquisition and Analysis Core at the Medical College of Virginia (MCV) campus also factored in my decision.”
Ott studies the effects of slow stretch mechanical cues. This represents the slow elongation of the anterior cruciate ligament, more commonly known as the ACL, during development or adolescence. The ACL plays an important part in stabilizing the knee by preventing the shin bone from moving forward on the thigh bone. Ott investigates these cues by applying slow stretch loading to high-density collagen hydrogels, literally stretching the material. This work is done through the lab of Jennifer Puetzer, Ph.D., biomedical engineering assistant professor. Creating engineered, lab-grown replacements for damaged tendons and ligaments is the lab’s primary goal. Injuries like ACL tears are common, and the hierarchical collagen fibers comprising these tissues do not repair themselves after injury. An individual with a torn tendon or ligament is unlikely to regain the same strength and function from it prior to injury.
“Cells are always in contraction,” Ott said. “They pull on their surroundings in collagen in our hydrogels. Undisturbed, cells pull the collagen toward themselves into a useless ball. It’s similar to a game of tug-o-war. If one side pulls with no one at the other end, you end up with a pile of rope at your feet. However, clamping down on the hydrogel ends prevents it from moving and provides cells with resistance. The cells tug their surroundings in a way that organizes collagen in fibers and fascicles in a way similar to what we see in native tendons and ligaments. This organization requires tension. In order for this organization to happen, the “rope” must be taut. The act of stretching creates the environment that allows the collagen in our hydrogels to become like those naturally found in the human body.”
Puetzer’s lab seeks to create clinically-relevant replacements for ligaments, like ACLs, which requires more mature and organized collagen. Ott’s research explores whether additional mechanical cues, like slowly stretching hydrogels at rates similar to ACL growth rates, will induce more organization in the system.
“To give you an idea of the scale I’m working with, I stretch collagen gels at 0.1 mm a day,” said Ott. “This has a huge impact on tissues, enabling collagen fibers to organize in a more natural way. I really want to know why this small change creates such a large-scale effect. Collagen is found in nearly every tissue, not just tendons and ligaments, so my research can have far-reaching implications.”
While resources needed to create tissue constructs are available in Puetzer’s lab, analysis of those constructs require other tools. Understanding the fiber and fibril levels of collagen in Ott’s hydrogels inform her on the maturity of the collagen. Fortunately, Ott has access to the right equipment through units like the NCC.
“Assays are tests to determine biochemical composition of our hydrogels,” said Ott. “We can perform this in the lab, but I need access to confocal and scanning electron microscopy to look closer at the collagen in my hydrogels. All I need to do is walk my prepped samples across the street from my lab to the NCC, where both types of microscopy are available. The biochemical assays we do can tell us the levels of DNA, collagen and crosslinks to see if we have a mature sample. We also do tensile tests and stretch the hydrogels until they rip apart. Mature hydrogels are more stiff and require more force to tear.”
Tissue engineering is a technically challenging field with difficult processes that make missteps more likely. Ott credits Puetzer for the way she’s grown as a researcher. “Dr. Puetzer has always allowed me the opportunities I’ve needed to grow my capabilities as a biomedical researcher,” Ott said. “When I’ve made mistakes, Dr. Puetzer offers me the space and mentorship to learn where I went wrong and how to keep it from happening again.”
In academics, Ott likes that graduate-level coursework facilitates more conversation between professors and students. Regenerative Engineering, one of her favorites, is among these subjects. “It was a more open environment than I’d seen in my undergraduate courses,” Ott said. “Discussing pertinent topics in regenerative engineering meant I had to thoroughly understand the topics involved, rather than just memorize them for a test.”
Ott also appreciates the flexibility in electives her program offers. Biomedical Signals Processing is a course outside her normal research focus that Ott enrolled in out of curiosity. It ended up helping more than she expected. “Not six months after I’d finished the course, I started a new research project that required me to use nearly every skill I’d learned in the class,” Ott said.
“From removing mechanical data noise to using digital filters to measuring fiber alignment and diameters in my images taken from confocal reflectance microscopy, I hadn’t done anything close to those techniques in the five years of research I conducted before taking that class. I really appreciate how my classes have prepared me for the real work I have to do for my research.”
When Ott isn’t working on research, she likes to put her biomedical engineering skills to use. She participated in an internship at Sheltering Arms Rehab Hospital and volunteered at an assistive technology service charity she discovered while working on her undergraduate Capstone project. Ott also enjoys the many experiences Richmond has to offer. “I’ve heard Richmond described before as a city with small-town vibes, and I think that really sums up my experience as well. There are so many events and things to do nearby, but it’s not as overwhelming as I’ve sometimes felt when I’ve gone to visit other cities.”
Aside from its research focused Ph.D. program, the Department of Biomedical Engineering now offers master’s degrees with concentrations in tissue engineering and regenerative medicine as well as rehabilitation engineering.
The Department of Biomedical Engineering provides undergraduate and graduate students with the opportunity to perform real-world research as soon as they enroll. From delving into the intricacies of cell migration in cancer research to exploring tissue engineering in menisci, tendons and ligaments, our students pursue a diverse range of cutting-edge research topics. Browse videos and recent news from the Department of Biomedical Engineering to discover how the College of Engineering at Virginia Commonwealth University prepares the next generation of scientists and engineers for the challenges of the future