3D printing technology is rapidly advancing and is being increasingly used for biological applications. The spatial control of 3D printing makes it especially attractive for fabricating 3D tissues and for studying the role of geometry in biology. We utilized two different types of 3D printing to engineer vascularized tissues with complex vascular architectures, to use engineered vasculature to treat ischemia, and to study directional endothelial cell migration on curved wave topography.
To engineer 3D tissues, perfusable vascular networks must be embedded within the tissue to supply nutrients and oxygen to cells. 3D-printed sugar filaments have previously been used as a cytocompatible sacrificial template to rapidly cast vascular networks. We improved upon the 3D-printed sugar method and used it to fabricate complex vascular geometries that were not previously possible, such as a branched channel geometry, with controlled fluid flow through the channels. We also integrated an approach utilizing vascular self-assembly to generate thick tissues with dense, capillary-scale vessel networks. The vascularized tissues fabricated using 3D-printed sugar successfully integrated with a host vasculature upon implantation and restored perfusion in two different animal models of ischemia.
Cell migration critical to numerous biological processes can be guided by surface topography. However, fabrication limitations constrain topography studies to geometries that may not adequately mimic physiological environments. Direct Laser Writing (DLW) provides the necessary 3D flexibility and control to create well-defined curved waveforms similar to those found in physiological settings, such as the lumen of blood vessels. We found that endothelial cells migrated fastest along square waves, intermediate along triangular waves, and slowest along sine waves and that directional cell migration on sine waves decreased at longer sinusoid wavelengths. Interestingly, inhibition of Rac1 decreased directional migration on 3D sine waves but not on 2D micropatterned lines, suggesting that cells may utilize different molecular pathways to sense curved topographies. Our study demonstrates that DLW can be employed to investigate directional migration on a wide array of surfaces with curvatures that are unattainable using conventional manufacturing techniques. / 2020-10-22T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/32074 |
| Date | 22 October 2018 |
| Creators | Cheng, Daniel |
| Contributors | Chen, Christopher S. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | Attribution-NonCommercial-ShareAlike 4.0 International, http://creativecommons.org/licenses/by-nc-sa/4.0/ |
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