A unit cell based multi-scale modeling and design approach for tissue engineered scaffolds
Authors:   , Gomez Connie , Sun Wei , Shokoufandeh Ali 
Published: July 2021

"'Tissue engineering is the application of principles and methods of engineering and life sciences toward the fundamental understanding of structure-function relationships in normal and pathological mammalian tissues and the development of biological substitutes to restore, maintain, or improve tissue function"' [35]. One key component to tissue engineering is using three dimensional (3D) porous scaffolds to guide cells during the regeneration process. These scaffolds are intended to provide cells with an environment that promotes cell attachment, proliferation, and differentiation. After sufficient tissue regeneration using in-vitro culturing methods, the scaffold/tissue structure is implanted into the patient, where the scaffold will degrade away, thereby leaving only regenerated tissue. The need to design these scaffold structures and the need for precision control during fabrication have lead to numerous challenges as well as to the development of the field of Computer Aided Tissue Engineering (CATE). CATE currently employs the application of computer aided technologies which have been tools within engineering and non-invasive medical imaging, namely, computer-aided design (CAD), computer-aided manufacturing (CAM), solid freeform fabrication (SFF), computed tomography (CT) and magnetic resonance imaging (MRI) for modeling, designing, and manufacturing man-made tissue replacements. Current CATE technologies are capable of producing intricate scaffolds with a great deal of control. Through the addition of existing tools from the field of computer science, the time required to design these intricate scaffolds and assess their ability to meet numerous design parameters can be greatly decreased. This thesis reports research that develops tools to further the abilities of tissue engineers to generate and fabricate biomimetic scaffold designs efficiently. The major accomplishments reported in this thesis include:1. Development of a framework of a unit cell based systematic approach for tissue scaffold design, including a unit cell informatics and property characterization crossing the unit cell structural scale levels based on the major design parameters.2. The establishment of criteria between 1D and 2D geometries for creating either material continuity or fluid pathway connectivity between unit cells within a scaffold.3. The development of an algorithm that will assemble unit cells such that within a tissue scaffold, unit cells are matched to specific regions based on design requirements and there is connectivity between adjacent regions.4. The development of a novel unit cell design approach, Volumetric Steiner Tree (VST), based on maintaining the underlying topology and therefore the connectivity of the unit cell. These novel approaches for modeling, designing and fabricating heterogeneous patient specific are possible by integrating existing computer science tools with existing CATE technologies. This research will also enable tissue engineers and cell biologists to expedite scaffold based tissue engineering research by minimizing the amount of human intervention required to design and fabricate either a heterogeneous scaffold with connectivity or a scaffold with prescribed design requirements.