Lucia Brunel: Biofabrication of Fibrillar Scaffolds for Tissue Engineering

Image

This past summer, I conducted research at the University of Würzburg thanks to generous support from the Stanford Club of Germany and The Europe Center. During my visit, I worked with Prof. Jürgen Groll, a leader in developing innovative biofabrication strategies to advance human health and the head of the Department for Functional Materials in Medicine and Dentistry (FMZ). Their institute’s mission aligns with my own Ph.D. research at Stanford, which focuses on 3D bioprinting cell-laden hydrogels. This technology has demonstrated great potential to mimic the macroscopic geometries of human tissues and organs. However, beyond achieving the complex geometry of native tissues, an important consideration is recapitulating the biological function of the tissue. Therefore, I hypothesized that incorporating biomechanical and biochemical cues within scaffolds would allow us to better guide cell behavior for enhanced tissue regeneration and function. The University of Würzburg was the ideal environment for me to explore this idea, due to FMZ’s state-of-the-art biofabrication and biochemistry facilities and the exceptional, interdisciplinary team of scientists and engineers there. 

Research Exchange

Tissues in the human body contain intricate nano- and micro-scale pores and fibers. These structural features are known to significantly influence cellular processes. Therefore, recapitulating native biomechanical and topographic cues in our bioengineered materials allows us to steer cell behavior toward their intended biological function. To create structured scaffolds, FMZ leverages advanced additive manufacturing techniques such as melt electrowriting. In the melt electrowriting process, a molten polymer is drawn from a syringe to a collector plate as a thin filament. Like a conventional 3D printer, the filament is then deposited in a programmed print pattern to achieve the desired scaffold. However, these filaments are still large in diameter compared to topographical features present in the extracellular matrix surrounding living cells in our bodies. Therefore, Prof. Groll’s laboratory recently pioneered a strategy of “melt electrofibrillation” to fabricate nanofiber bundles that mimic the fibrillar microstructures of native tissues. By using a polymer blend that includes a sacrificial component, the melt electrowriting process induces an oriented phase separation between the two polymers. The sacrificial polymer can then be selectively dissolved away to leave behind biomimetic nanofibrillar microbundles. These structural features are recognizable by cells and affect their behavior.

For my research project, I was interested in leveraging the fibrillar scaffolds that impart biomechanical cues and adding biochemical cues to further guide the phenotype of cells seeded in the scaffolds. Specifically, for bone tissue engineering, mineralized biomaterials have demonstrated enhanced bone regeneration. Therefore, we hypothesized that minerals could be added into our scaffolds to induce the differentiation of stem cells toward bone-like behavior. I found that minerals could be incorporated into the fibrillar scaffolds either by adding mineral particles directly into the polymer melt before melt electrowriting, or by forming a mineral coating on the scaffolds after melt electrowriting. In this project, I learned a wide variety of skills: melt electrowriting (MEW) parameter optimization to fabricate the scaffolds; scanning electron microscopy (SEM) to observe the scaffold structure; energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), Raman spectroscopy, and X-ray diffraction analysis (XRD) to characterize the minerals in the scaffold; inductively coupled plasma mass spectrometry (ICP-MS) to measure the ion release from the scaffold over time, and live/dead assays to quantify the viability of cells in the scaffold. The results from this study will help inform the design of instructive scaffolds that guide cell behavior for enhanced bone regeneration.

My research exchange in Germany extended beyond hands-on work in the laboratory. I had the opportunity to engage in scientific discourse with other top scientists and professors in the country, both at the University of Würzburg and at other universities. In Würzburg, I met with several professors within FMZ and other relevant departments. To share some of my recently published bioprinting research from Stanford with my colleagues in FMZ, I presented at the biofabrication subgroup’s weekly journal club. My talk was followed first by a lively research discussion, and second by an equally lively karaoke session! I also traveled to the University of Erlangen-Nuremberg and to Charité – Berlin University Medicine to tour the laboratories of three different research groups and meet with their students. It was interesting to learn about the organization of academic research in Germany and the prominent research thrusts within the biomaterials community in Germany. Additionally, I was fortunate to attend the 2023 European Society for Biomaterials (ESB) meeting in Davos, Switzerland, where I was selected to give an oral presentation on my bioprinting research. The conference was a highly interdisciplinary gathering of European scientists and engineers interested in applying materials science and engineering principles toward advancing human health. Through the Q&A discussion after my talk and follow-up conversations with attendees, I received valuable feedback and fresh perspectives on my research. From other speakers, I learned about the most recent, cutting-edge developments in our field across Europe. The conference also provided networking and/or social opportunities such a Young Scientist Night Out (at a restaurant on top of a mountain in the Alps!), a run around the Davos lake, a Gala dinner, and conference lunches over which I met many professors and students in person, some of whose work I was already familiar with and had admired for years, and others working on exciting projects of which I had not yet been aware. These experiences across Germany and at the ESB conference enriched my scientific perspective, expanded my personal and professional networks, and reinforced my excitement for contributing to advances in biomaterials for global health.

Cultural Exchange

One of the most special parts of living in Germany over the summer was the immersion in German life and engagement with their vibrant culture. Since FMZ is located in central Würzburg, surrounded by an abundance of restaurants, my labmates and I would often go out for lunch to chat and enjoy a nice meal together. In the evenings, many wine festivals came alive at surrounding wineries or in the city center plaza. Würzburg, being in the Franken wine region in Bavaria, is known for its white wines such as Silvaner, Müller-Thurgau, Riesling, Bacchus (my favorite!), and Scheurebe. I enjoyed meeting up with friends in the evenings to try a glass of wine together, usually poured from a bocksbeutal—a distinctively short and flattened wine bottle characteristic of Franconian wines. Over the weekends, I explored the sights around Würzburg, which included the Würzburg Residenz (a stunning palace and UNESCO World Heritage Site), the Festung Marienburg (a fortress perched on the hill overlooking the city and surrounding hills), and the Alte Mainbrücke (a pedestrian bridge on the Main river lined with statues of saints).

I was also fortunate to take a few weekend trips outside of Würzburg, facilitated by the well-connected train network in Germany. I spent one weekend visiting friends in Munich, which is not only a beautiful and historical city for Germany but also for my own family! My parents first met each other there many years ago when they were both studying German language in Munich. I even got to send them a picture of me at the Fischbrunnen, a fountain in the center of Munich and the meeting point for their first date! Apart from Munich, I spent a weekend in Berlin, where I met up with Justin, another GRIP scholar. We had a great time exploring the city and visiting historical sites. We also happened to be there during the “Lange Nacht der Museen,” during which dozens of museums around Berlin were open until 2 am, and admission to all of them was included within a single ticket! Finally, I got to indulge in German food and drinks all summer—from döner kebab and currywurst to apfelschorle and radlers.

Conclusions

Pursuing a research project in Germany this summer was a transformative experience that enriched both my academic and personal growth. The exposure to a new academic environment, diverse cultural perspectives, and advanced research methodologies significantly contributed to my development as a scholar and prepared me for the challenges and opportunities that lie ahead in my future career as a globally minded scientist and leader. I was able to broaden my perspective on how biomedical research is operated in countries with different policies, priorities, and frames of reference, which I believe is essential for fostering innovation and collaboration on an international scale. I am sincerely grateful to GRIP for providing the invaluable support that made this journey possible, facilitating both my research and cultural immersion in Germany. I am already looking forward to my next trip to Germany!