My name is Gabriel David, and I am a biomedical engineering student leading a research project to improve peripheral nerve repair underneath my mentor Dr. Young Hye Song. My fellow researchers and I aim to create collagen-based scaffolds that will allow enhanced nerve repair via aligned collagen fibers as well as stem cell-derived cues within the scaffold. More than 20 million Americans are afflicted with some form of peripheral neuropathy, making research into methods to fix these problems essential for the medical field.

Research involving nerves is both fascinating and complicated. Dozens of environmental factors play significant roles in nerve development, some of which are yet to be discovered. My project aims to create the optimal environment for nerve repair by mimicking the natural conditions peripheral nerves would grow in with added benefits coming from encapsulated stem cells. To do this, we are making aligned 3D collagen scaffolds containing mesenchymal stem cells (MSCs). We have high expectations for this to improve on earlier methods of nerve regeneration for multiple reasons, where current gold standards are hollow nerve guidance conduits that provide no physical guides to the regenerating neurons. First, collagen is one of the main components of the human extracellular matrix, including peripheral nerves. Second, MSCs are also very important because they provide physicochemical cues necessary for nerve repair. Studies have shown that the existence of physical guidance in the nerve repair scaffolds, as well as MSC-derived neuro-regenerative cues, are beneficial in successful peripheral nerve repair.

At the end of the Fall 2020 semester, we have made substantial progress even with many roadblocks, including limited research time due to the COVID-19 pandemic, along the way. These hurdles were time consuming and have caused some slight delay in progress. The three most significant issues were the creation of type I collagen scaffolds, silicone sheets, and stretching device. At the beginning of the semester, we had successfully made a batch of collagen, but found out later that the scaffolds were not forming properly. This was a critical issue, as these scaffolds could be deemed the backbone of this project. Over time and with assistance of our graduate students, Emory Gregory and Inha Baek, we developed a new protocol that resulted in reproducible collagen scaffold formation. The next issue arose during the stretching of the scaffolds using silicone-based molds. While the first stretching sessions worked out well, the last experiment had all of our replicates snap under tension. To fix this problem, we optimized the mold composition. We found that by increasing the ratio of the silicone elastomer base to the curing agent, the sheets were much more resilient and could handle much more than the required amount of stretch. Finally, I designed our custom stretching device that was needed primarily due to scheduling conflicts with using another lab’s automated uniaxial stretching device. By working with Mr. Jeff Knox at the Engineering Research Center where the Song lab is located, I drew a CAD sketch of the device, researched proper materials and created the stretching device that allow different levels of static strain.

Despite world health concerns and these setbacks, the progress we have made in Fall 2020 is substantial. During this semester we have perfected the creation of the collagen scaffolds, silicone sheets, stretching device, and even learned to culture human MSCs with no cases of contamination. We had intended to perform in vitro analysis of MSC-containing collagen scaffolds before the start of the Spring 2021 semester, but due to the setbacks listed we were not able to keep that timeline. This should not be a major issue, however, as we should still be able to complete all the future steps before the end of the Spring 2021 semester.

I would like to thank all the members of the Song lab, as well as the members of the Balachandran lab that assisted in the creation of the stretching device and the Quinn lab for imaging of the collagen scaffolds. Without the assistance of these fine people, and the many more to come, this project would not have been able to progress this fast.

For the future directions, we have the biggest step of the entire project. As mentioned above, characterizing MSC-containing collagen scaffolds in vitro will make up the bulk of the Spring 2021 semester. This is where the quantitative data that determines the success or failure of the project will come from. We have high hopes for the outcome of this study that at the very least will provide a strong foothold for future projects focused on collagen scaffold-based nerve repair.