Author: David Gabriel     Major: Biomedical Engineering 

Casting and stretching collagen gels

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 nerve-mimetic topography 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.

Continuing from the Fall 2020 semester, we have made substantial progress in the Spring 2021 semester even with many roadblocks, including limited research time due to the COVID-19 pandemic, along the way. We solved our PDMS and collagen gelation problems by sourcing thin silicone sheets and improving our collagen collection protocols. These improvements have allowed us to successfully create aligned MSC containing gels. These gels were then cultured for a week and subsequently analyzed. It was found that there was a significant difference in alignment between stretched and non-stretched samples when comparing both collagen fibers and the cells while still maintaining cell viability. This is a very important accomplishment for the progress of this research project, but there are still very many aspects that must be investigated. This includes the most important aspect of whether these aligned collagen scaffolds improve nerve regeneration when compared to non-aligned samples.

As mentioned above, there are many more things to investigate in the future. The next steps our lab will take is to research the effects different gel concentrations have on the scaffolds as well as running assays to determine the presence of common MSC environmental cues. After we determine which groups show optimal results, we will begin to culture neurons with these scaffolds to measure neurite outgrowth and compare aligned and non-aligned samples. Should these experiments show desirable results, in-vivo studies are being considered.

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.