Browsing by Subject "biofabrication"

Now showing 1 - 3 of 3
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    Agent-Based Numerical Methods for 3D Bioprinting in Tissue Engineering
    (Elsevier, 2018) Sego, T. J.; Moldovan, Nicanor I.; Tovar, Andres; Mechanical Engineering, School of Engineering and Technology
    Additive manufacturing has contributed significantly to the development of new surgical and diagnostic aids, personalized medical devices, implants, and prostheses. Now, it aspires to the direct digital manufacturing of living tissue, organs, and body parts. This can be achieved using three-dimensional (3D) bioprinting techniques in which the printing medium consists of biomaterials and living cells. Several 3D bioprinting methods are currently available, including inkjet, extrusion, and stereolithography. An emerging approach is the creation three-dimensional cellular patterns by the use of cell spheroids. The optimal application and further development of 3D bioprinting techniques could largely benefit from computational models capable of predicting the complex behavior of the printed cellular structures on multiple scales. This book chapter summarizes the state of the art of computational models in this field, with an emphasis on agent-based approaches and cell spheroid-based 3D bioprinting.
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    A Heuristic Computational Model of Basic Cellular Processes and Oxygenation during Spheroid-Dependent Biofabrication
    (IOP, 2017) Sego, T. J.; Kasacheuski, Uladzimir; Hauersperger, Daniel; Tovar, Andres; Moldovan, Nicanor I.; Biomedical Engineering, School of Engineering and Technology
    An emerging approach in biofabrication is the creation of 3D tissue constructs through scaffold-free, cell spheroid-only methods. The basic mechanism in this technology is spheroid fusion, which is driven by the minimization of energy, the same biophysical mechanism that governs spheroid formation. However, other factors such as oxygen and metabolite accessibility within spheroids impact on spheroid properties and their ability to form larger-scale structures. The goal of our work is to develop a simulation platform eventually capable of predicting the conditions that minimize metabolism-related cell loss within spheroids. To describe the behavior and dynamic properties of the cells in response to their neighbors and to transient nutrient concentration fields, we developed a hybrid discrete-continuous heuristic model, combining a cellular Potts-type approach with field equations applied to a randomly populated spheroid cross-section of prescribed cell-type constituency. This model allows for the description of: (i) cellular adhesiveness and motility; (ii) interactions with concentration fields, including diffusivity and oxygen consumption; and (iii) concentration-dependent, stochastic cell dynamics, driven by metabolite-dependent cell death. Our model readily captured the basic steps of spheroid-based biofabrication (as specifically dedicated to scaffold-free bioprinting), including intra-spheroid cell sorting (both in 2D and 3D implementations), spheroid defect closure, and inter-spheroid fusion. Moreover, we found that when hypoxia occurring at the core of the spheroid was set to trigger cell death, this was amplified upon spheroid fusion, but could be mitigated by external oxygen supplementation. In conclusion, optimization and further development of scaffold-free bioprinting techniques could benefit from our computational model which is able to simultaneously account for both cellular dynamics and metabolism in constructs obtained by scaffold-free biofabrication.
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    Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment
    (MDPI, 2020-11) Wendel, Jillian R. H.; Wang, Xiyin; Smith, Lester J.; Hawkins, Shannon M.; Obstetrics and Gynecology, School of Medicine
    Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be of a specific diameter (~500 μm), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNFα stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.