Grace Hu1,Zeqing Jin2,Austin Graham3,4,Zev Gartner1,3,4,Grace Gu1,2
University of California, Berkeley & San Francisco1,University of California, Berkeley2,University of California, San Francisco3,Chan Zuckerberg Biohub4
Grace Hu1,Zeqing Jin2,Austin Graham3,4,Zev Gartner1,3,4,Grace Gu1,2
University of California, Berkeley & San Francisco1,University of California, Berkeley2,University of California, San Francisco3,Chan Zuckerberg Biohub4
3D-bioprinting facilitates the construction of scaffolds with complex geometries and at high precision. Design and process parameters for 3D-bioprinted materials must be carefully considered and characterized for each specific application.<sup>[1]</sup> Given the critical mechanical and physiological roles of type I collagen and laminin within the native extracellular matrix (ECM), we investigate how the printability and stiffness of composites of type I collagen and laminin is controlled through various printing process parameters. Numerical simulations are first implemented to characterize the swelling behavior of collagen, which are then compared to experimental testing. With an eye towards translation and ease-of-use, we utilize the commercially-available CellInk BioX bioprinter to control infill density, concentration, nozzle diameter, and heating duration throughout printing, observing vastly different mechanical properties in the resultant hydrogels.<br/>Building from this work, we also seek to establish a reliable framework for 4D-bioprinting, in which the structure undergoes programmable mechanical and biochemical transformations over time. To this end, we computationally analyze and experimentally validate origami-inspired tissue folding mechanisms. Mouse embryonic fibroblasts (MEFs) are employed due to their contractile behavior that can be predictably modeled using finite element methods.<sup>[2]</sup> Collagen-Matrigel composites are prepared to investigate how MEF clusters contract the surrounding matrix as a function of material stiffness and mechanical cell state. The MEFs exhibit excellent cell viability, proliferation, and ability to dependably remodel the matrix over 24 hours. Ultimately, these results inform strategies for 4D tissue printing for biofabrication, developmental models, and regenerative medicine.<br/><br/>[1] Aldana, A., Valente, F., Dilley, R., & Doyle, B. (2021). Development of 3D bioprinted GelMA-alginate hydrogels with tunable mechanical properties. <i>Bioprinting</i>, <i>21</i>(e00105), 1-9. doi: 10.1016/j.bprint.2020.e00105<br/>[2] Hughes, A., Miyazaki, H., Coyle, M., Zhang, J., Laurie, M., & Chu, D. et al. (2018). Engineered tissue folding by mechanical compaction of the mesenchyme. <i>Developmental Cell</i>, <i>44</i>(2), 165-178. doi: 10.1016/j.devcel.2017.12.004