CAD has been traditionally used to assist in engineering design and modeling for representation, analysis and manufacturing. Advances in Information Technology and in Biomedicine have created new uses for CAD with many novel and important biomedical applications, particularly in tissue engineering in which the CAD based bio-tissue informatics model provides critical information of tissue biological, biophysical, and biochemical properties for modeling, design, and fabrication of complex tissue substitutes. This paper will present some salient advances of bio-CAD modeling and application in computer-aided tissue engineering, including biomimetic design, analysis, simulation and freeform fabrication of tissue engineered substitutes. An overview of computer-aided tissue engineering will be given. Methodology to generate bio-CAD models from high resolution non-invasive imaging, the medical image process and the 3D reconstruction technique will be described. Enabling state-of-the-art computer programs in assisting 3D reconstruction and in bio-model development will be introduced. Utilization of the bio-CAD model for the description and representation of the morphology, heterogeneity, and organizational structure of tissue anatomy will also be presented.