Christina Hummel is originally from Long Island, New York. She attends Clemson University in South Carolina, where she studies bioengineering and chemistry. She is currently working in Dr. Jason Burdick’s Polymeric Biomaterials lab with Dr. Claudia Loebel. Through the REU program, she will be working to optimize hydrogels for therapeutic applications in patients who are suffering from lung fibrosis. In the future, Christina would like to work on researching and developing new therapies for disease.
Microstructured Hydrogels for Controlled Formation of Bronchial Organoids
Epithelial organoids are emerging as cell culture platforms for epithelial tissue disease modeling and regenerative therapy such as in acute and chronic lung injuries. However, current organoid systems are traditionally based on mixed cultures with mesenchymal cells. These approaches limit understanding mesenchyme-epithelial cell paracrine signaling events during epithelial organoid formation as well as contributions of biophysical cues such as matrix mechanics and topography. Thus, we designed a synthetic hydrogel platform containing microwells to generate lung epithelial organoids physically separated from mesenchymal cells and within a microenvironment that mimics aspects of the native distal lung microenvironment. The hydrogels were fabricated from norbornene-modified hyaluronic acid with various microwell sizes and a range of different elastic moduli with high patterning fidelity. Human lung fibroblasts (hLFs, Lonza) were encapsulated in the hydrogels at 5 million cells/mL and human bronchial epithelial cells (hBECs, Lonza) were seeded at 66 cells per microwell. Hydrogels promoted the formation of hBECs spheroids when cultured in 500/200 μm microwells, which depended on hydrogel mechanics. When compared to larger microwells (800/300 μm) hBECs formed organoid-like structures with higher cell viability and increased diameter after 3 days, indicating that matrix topography guides hBEC self-assembly and organization. The fabrication of microstructured hydrogels facilitated the formation of epithelial cell organoids physically separated from the mesenchymal cell population. Both microwell size and hydrogel stiffness determined cell fate, viability, and overall epithelial cell organoid formation, which can be extended to the generation of other epithelial organoids. Future work will elucidate the contribution of matrix mechanics and degradability and extend to alveolar epithelial cells for therapeutic applications.