Veiseh, Omid2022-09-262022-052022-04-22May 2022Parkhideh, Siavash. "Design and Evaluation of Vascularizing Scaffolds Towards Multi-compartment Engineered Tissues." (2022) Diss., Rice University. <a href="https://hdl.handle.net/1911/113373">https://hdl.handle.net/1911/113373</a>.https://hdl.handle.net/1911/113373EMBARGO NOTE: This item is embargoed until 2024-05-01Tissue engineering research and the goal of developing thick replacement tissues such as heart, liver, and lung require the creation of a functional vascular network. Specifically, naturally occurring vasculature is hierarchical and spatially patterned. Prior work has previously shown that patterned vasculature can enhance engineered tissue function and limb perfusion. While various methods can promote the development of patterned vasculature, bioprinting was used in these studies due to its ability to fabricate complex, multivascular structures. To allow for modular and tissue-agnostic design, we designed and fabricated core-shell hydrogel structures with a non-degradable hydrogel core, containing stromal cells (i.e., the stromal compartment), and a degradable hydrogel shell containing perfusable, patterned vascular structures (i.e., the vascular compartment). Initial studies demonstrated that vascular architectures with stromal cells located within the plane of the vasculature resulted in enhanced nutrient delivery between vascular and stromal compartments. Laminar flow was detected within bioprinted channels, beneficial for channel endothelialization and consistent wall shear stress. Then, vascular cells were printed within the hydrogel matrix and seeded into the bioprinted channels and cultured under perfusion over multiple days. Perfusion culture allowed endothelial cell maintenance, and in co-culture hydrogels, lead to cell-cell coordination within the construct in vitro. Notably, the greatest degree of biomaterial vascularization and influence over vascular patterns was seen within hydrogels fabricated with RFP HUVECs and hMSCs encapsulated within the bulk hydrogel, along with GFP HUVECs lining the walls of the patterned channels, maintained in perfusion culture for three days. Finally, for this optimal formulation, vascularization was detected as early as two weeks, and vessels up to 100 µm in diameter had formed by eight weeks, demonstrating vessel development and maturation over time. The ability for spatially controlled endothelial structures to influence vascular patterning in vivo can inform future studies in developing thick, vascularized tissues and organs. Furthermore, we fabricate retrievable, immunoisolating hydrogels to comprise the stromal compartment and determine that islets maintain viability, functionality, and ability to restore normoglycemia within these matrices.application/pdfengCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.angiogenesistissue engineeringbioprintingislet transplantationThesis2022-09-26