Browsing by Author "Parkhideh, Siavash"

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    Design and Evaluation of Vascularizing Scaffolds Towards Multi-compartment Engineered Tissues
    (2022-04-22) Parkhideh, Siavash; Veiseh, Omid
    Tissue 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.
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    Perfusable cell-laden matrices to guide patterning of vascularization in vivo
    (Royal Society of Chemistry, 2023) Parkhideh, Siavash; Calderon, Gisele A.; Janson, Kevin D.; Mukherjee, Sudip; Mai, A. Kristen; Doerfert, Michael D.; Yao, Zhuoran; Sazer, Daniel W.; Veiseh, Omid
    The survival and function of transplanted tissue engineered constructs and organs require a functional vascular network. In the body, blood vessels are organized into distinct patterns that enable optimal nutrient delivery and oxygen exchange. Mimicking these same patterns in engineered tissue matrices is a critical challenge for cell and tissue transplantation. Here, we leverage bioprinting to assemble endothelial cells in to organized networks of large (>100 μm) diameter blood vessel grafts to enable spatial control of vessel formation in vivo. Acellular PEG/GelMA matrices with perfusable channels were bioprinted and laminar flow was confirmed within patterned channels, beneficial for channel endothelialization and consistent wall shear stress for endothelial maturation. Next, human umbilical vein endothelial cells (HUVECs) were seeded within the patterned channel and maintained under perfusion culture for multiple days, leading to cell–cell coordination within the construct in vitro. HUVEC and human mesenchymal stromal cells (hMSCs) were additionally added to bulk matrix to further stimulate anastomosis of our bioprinted vascular grafts in vivo. Among multiple candidate matrix designs, the greatest degree of biomaterial vascularization in vivo was seen within matrices fabricated with HUVECs and hMSCs encapsulated within the bulk matrix and HUVECs lining the walls of the patterned channels, dubbed design M-C_E. For this lead design, vasculature was detected within the endothelialized, perfusable matrix channels as early as two weeks and αSMA+ CD31+ vessels greater than 100 μm in diameter had formed by eight weeks, resulting in durable and mature vasculature. Notably, vascularization occurred within the endothelialized, bioprinted channels of the matrix, demonstrating the ability of bioprinted perfusable structures to guide vascularization patterns in vivo. The ability to influence vascular patterning in vivo can contribute to the future development of vascularized tissues and organs.