The field of tissue engineering brings together the multidisciplinary research of life sciences and engineering to seek man-made substitutes for the regeneration of damaged tissue or organs. A key component in tissue engineering is the use of porous scaffolds to guide cells for attachment, proliferation and differentiation in the tissue regenerative process. Upon satisfactory in-vitro culture, this engineered living scaffold is implanted into the regeneration site of the patient to function as the tissue substitute. Conventional processing techniques for the fabrication of scaffolds often encounter difficulties in the precise control of the internal architecture, interconnectivity and distribution of pores within the scaffold. These challenges, along with the advances in biology, medicine, and information technology for tissue engineering applications, have led to the development of a new field of Computer Aided Tissue Engineering (CATE).CATE enables a systematic application of computer-aided technologies, i.e., computer-aided design (CAD), image processing, computer-aided manufacturing (CAM), and solid freeform fabrication (SFF) for modeling, designing, simulation, and manufacturing of biological tissue and organ substitutes. Through the use of CATE, the design of intricate three dimensional architecture of scaffold can be realized and these scaffolds can be fabricated with reproducible accuracy to assist biologists in studying complex tissue engineering problems. This thesis reports a research addressing some of the challenges in applying the CATE approach for the biomimetic design and freeform fabrication of tissue scaffolds. The major research accomplishments reported in this thesis include: a) The development of a BioCAD modeling technique for the design and representation of patient specific 3D tissue models based on non-invasive medical image data. b) The development of a biomimetic design approach for design of load bearing tissue scaffold subject to multiple biophysical, geometrical and manufacturing requirements. This includes the design of the unit cell micro-architecture based on tissue morphologies, unit cell characterization and evaluation of the mechanical and transport properties, and the use of unit cells as building block to design anatomic tissue scaffold replacements. c) The development of a CAD based path planning procedure through a direct slicing algorithm which can convert a neutral ISO (International Standards Organization) standardized STEP (Standard for the Exchange of Product Data) formatted NURBS (Non-Uniform Rational B-Spline) geometric representation to a tool path instruction set for layered freeform fabrication. d) The development of a novel Internal Architecture Design (IAD) approach for the mapping of characteristic patterns of the unit cell micro-architectures designed within the 3D scaffold. This design approach is implemented into a process algorithm that converts these 2D patterns to tool path datasets for the 3DP™ (threedimensional printing) and extrusion based freeform fabrication.CATE enables many novel approaches in modeling, design, and fabrication of complex tissue substitutes with enhanced functionality for research in patient specific implant analysis and simulation, image guided surgical planning and scaffold guided tissue engineering. The research will also enable cell biologists and engineers to expand their scope of research and study in the field of tissue engineering and regenerative medicine.Ph.D., Mechanical Engineering -- Drexel University, 200
