Approximately 175,000 reconstructions of torn anterior cruciate ligaments (ACL) are performed each year in the United States. Yet even with this high frequency, 10 percent of the surgeries result in the failure of a key component of the procedure: a skin graft to replace the torn ligament. A Florida Tech doctoral student is researching ways to improve ACL reconstruction outcomes.
Nashaita Patrawalla, a Ph.D. candidate in biomedical engineering, is working on ACL reconstruction applications in the Kishore Lab, led by Vipuil Kishore, associate professor in the department of biomedical and chemical engineering and sciences.
In an ACL construction procedure, a graft is used to replace the torn ligament. The graft can be obtained from the patient, such as their hamstring, can be synthetic or could come from a cadaver. Patrawalla is focusing on reconstructing the ACL “enthesis,” which is the transition region from the ligament to the bone. The native ACL ends are a complex region made up of different cell types, having different mechanical properties along the enthesis, and a gradient of mineral composition which ensures the smooth transition of load from the ACL to bone.
However, in reconstructed ACLs, the enthesis region is absent due to the injury, which increases the chances of re-tears. Patrawalla uses 4D-printing techniques to produce a functional ACL enthesis to be attached at the ends of grafts to allow for better integration at the ligament-to-bone transition region. This greatly reduces the risk of re-tears and additional injuries.
“A successful ACL reconstruction demands reproducing a functional ACL enthesis, which is the focus of my work,” she said.
Identifying properties of native tissues, such as alignment of the collagen fibers, is a crucial factor that impacts aspects like cellular response, which is important for tissue regeneration. Researchers in Kishore’s lab are looking at different alignment techniques for collagen fibers. Patrawalla’s work focusses on developing a method which combines magnetic field application with 3D-printing techniques to provide a 4D printing platform. The hypothesis is that by adjusting the magnetic field and how it’s applied to these scaffolds of manufactured tissue, highly aligned collagen matrices will be obtained. This differs from regular fabrication techniques where the alignment wouldn’t be possible, which is an important cue for cell differentiation and is currently lacking for proper tissue regeneration. Using collagen for the grafts, Patrawalla is also looking at how the fibers are orientated and the best procedures to ensure the grafts don’t fail.
“With regular 3D printing of collagen, the fibers would orient randomly, which would impact the mechanics and cell response,” she said. “When you achieve alignment of the fibers within the graft, it has the potential to improve some of the properties by resembling the native tissue closely and by providing cues for expedited tissue regeneration.”
There are different aspects that can be focused on regarding ACL enthesis regeneration. Prior work from the Kishore Lab, led by Florida Tech alumnus Nilabh Kajave, used different concentrations of bioceramics to generate the gradient in mineral composition on the tissue-engineered scaffold. Patrawalla, as part of her master’s thesis work, studied different bioceramics to identify the one with greatest potential for osteogenic differentiation. That’s the process where stem cells transform into a bone-forming cells
type. Future projects in the lab will involve testing the ACL enthesis in rabbit models, with the goal of getting the process adopted into clinical settings.
While Patrawalla has been working on this project for some time, the research took on added meaning over the last two years. Seven days into 2022, she reinjured her ACL and ended up getting ACL revision surgery. Seven days into 2023, she successfully defended her doctoral proposal which focuses on ACL enthesis reconstruction applications.
“I definitely feel very connected to my project, and there’s a lot of internal motivation towards completing the aims of my proposed research,” she said. “This work has the potential to impact numerous individuals, which drives me to seek the answers to the questions that pose as current challenges in the field.”