In this project, a commercial 3-D inkjet printer, a representative Rapid Prototyping (RP) system, was employed to produce collagen scaffold using an indirect, sacrificial mould method. This method offers a great degree of design freedom compared to conventional as well as direct RP-fabrication method. To better understand the inkjet printing process, a physical model was established to relate the operating parameters to the dimensions of the part printed. The ability to control the parameters is important in order to achieve the predetermined morphology and resolution of the mould in this indirect fabrication technique. One major challenge in scaffold-based tissue engineering has been the limitation of cell migration and tissue ingrowth within the scaffolds. In this research, networks of channels were incorporated into the matrix as part of the architecture to overcome the limitation of nutrient diffusion. The shape, dimension, distribution, configuration as well as the orientation of the channels can be easily designed and controlled. The calculations of the channels lengths were performed based on the estimated flow shear in the channels and the oxygen mass balance required in the scaffold. An analytical model is presented to illustrate the enhancement of cell proliferation in scaffold with the internal channels. In vitro cell culture experiments with Human Primary Osteogenic Sarcoma (SaOS-2) cells were performed on control collagen scaffolds without internal channels and RPfabricated collagen scaffolds with internal channels. Cell Proliferation Assay studies showed significantly more cells were attached within the scaffolds with internal channels and these cells were distributed more homogenously. Scanning electron microscopy analysis and histological analysis confirmed that cells were attached in the interior region of the RP scaffolds. Higher cell penetration depth was also observed in the scaffolds through this improved technique. A customized direct perfusion bioreactor for the cultivation of cells on compliant scaffold was developed successfully. Significantly higher cell density was recorded in direct perfusion cultured scaffolds compared to the static cultured ones. The 1 ATTENTION: The Singapore Copyright Act applies to the use of this document. Nanyang Technological University Library combination of a RP-fabricated collagen scaffold and the direct perfusion bioreactor was able to maximize the proliferation of cells in scaffold and enhanced homogeneous distribution of cells. II