Continued scientific research is crucial for developing new biomedical products, such as tissue engineering scaffolds, that are difficult to optimize due to the complexity of interfacing mechanical and biological systems. In this paper, mechanical and biological perspectives are used to propose and implement an approach for designing hierarchical scaffolds that provide structural support in the body as tissue regenerates. Three sequential steps are proposed for defining design needs, generating design alternatives, and fabricating design prototypes. Design needs are determined by considering mechanical and biological performance requirements, experimental procedures, and fabrication constraints. The primary mechanical requirement is a scaffold's need to maintain structural integrity, while biologically the scaffold should promote cellular growth. Scaffold design alternatives of four topology types are generated by altering design parameters that describe a scaffold's structure. Trade-offs are revealed for scaffold porosity and surface area properties that are known to influence mechanical and biological scaffold performance. Scaffolds of each topology type are designed with 80% porosity and fabricated, which enables their potential use in scientific experiments to measure how property trade-offs influence scaffold performance. On the basis of currently available knowledge, a to-scale spinal scaffold implant is designed and fabricated with a graphically maximized surface area to porosity ratio for a hierarchical scaffold, which represents a potentially high performing design from both mechanical and biological perspectives. These results demonstrate the importance of multidisciplinary approaches for designing complex biomedical tissue scaffolds that could significantly improve healthcare through the development of new clinical products.