One of the greatest challenges in regenerative medicine is generating clinically-relevant engineered tissues with functional blood vessels. Vascularization is a key hurdle faced in designing tissue constructs larger than the in vivo limit of oxygen diffusion. In this study, we utilized fibrin-based hydrogels as a foundation for vascular formation, poly(ethylene glycol) (PEG) to modify fibrinogen and increase scaffold longevity, and human amniotic fluid-derived stem cells (AFSC) as a source of vascular cell types (AFSC-EC). AFSC hold great potential for use in regenerative medicine strategies, especially those involving autologus congenital applications, and we have shown previously that AFSC-seeded fibrin-PEG hydrogels have the potential to form three-dimensional vascular-like networks in vitro. We hypothesized that subcutaneously injecting these hydrogels in immunodeficient mice would both induce a fibrindriven angiogenic host response and promote in situ AFSC-derived neovascularization. Two weeks post-injection, the average maximum invasion distance of host murine cells into the subcutaneous fibrin/PEG scaffold was 147±90µm after one week and 395±138µm after two weeks, the average number of cell-lined lumen per mm 2 was significantly higher in hydrogels