Deep, chronic wounds are a prevalent clinical concern caused by injury or trauma to the skin and underlying soft tissues such as fat, vasculature, fascia, muscle, and even bone. Fat is one of the most abundant and key tissue types necessary for soft tissue reconstruction (STR) and is harvested via autologous fat transfer (AFT), which is the resection and reallocation of adipose tissue from a healthy donor region to the defect site. While these procedures are effective, they are limited by donor-site morbidity, post-operative debilitation, risk of infection and necrosis, and donor tissue availability. 3D-bioprinting and tissue engineering strategies provide a promising solution to address these shortcomings. However, in order to adequately fabricate tissues for regenerative medicine, perfusable and hierarchical vasculature must be incorporated. Additionally, a more robust understanding of matrix mechanics, such as stiffness and viscosity, is crucial to recapitulating the material properties that support fat and vascular formation. Thus, there is a need to establish a tunable system capable of bioengineering fat and other clinically relevant tissues with patent vasculature as an alternative to AFT and other STR procedures. The objective of this work was to examine the vascular and adipogenic potential of endothelial and adipose stem cells within a tunable matrix for macro-perfusion and STR. First, we synthesized and utilized a mechanically tunable bioink, gelatin methacryloyl, to examine the role of matrix stiffness and viscosity on adipogenesis and vasculogenesis. Next, we developed a macro-perfusion bioreactor (MPB) system that can support the fabrication of large constructs with patent and high-throughput lumen geometry (the Squiggle). Finally, we build upon our MPB system, harboring the Squiggle channel design, to elucidate the impact of hemodynamic shear stress and vorticity on bulk diffusion and endothelium maturation, which will eventually serve as a platform to study the effects of hemodynamic flow on angiogenesis. Altogether, the hope is that the knowledge gained from this work and the establishment of a model MPB system can be adapted to engineer fat and other heterogenous tissues with patent and hierarchical vasculature for STR and regenerative medicine.