[EMBARGOED UNTIL 6/1/2023] With the success of solid organ transplantation, a next generation approach has been developed known as vascularized composite allografts which requires the transplantation of a whole functional unit comprised of many tissues including skin, bone, muscles, blood vessels, and nerves as a single unit from a deceased donor to the patient. However, similar to other solid organ transplants, the biggest challenge associated with vascularized composite allografts is their post-surgery acute rejection. To prevent and alleviate this problem, broad-spectrum immunosuppressants are required which unfortunately have two major disadvantages: (1) low on-target efficiency and/or severe adverse side effects and (2) require conventional oral and subcutaneous administration routes that can lead to systemic immunosuppression, which together increase the risk of infection or developing cancer. To address the first problem, I studied a promising biocompatible and immunomodulatory biologic -- vasoactive intestinal peptide and designed vasoactive intestinal peptide amphiphile micelles with different chemical formulations, shapes, and sizes to determine factors that influence the bioactivity of this peptide therapeutic. While specifically important for the development of novel immunosuppressant therapies, the impact micellar physical properties have on incorporated bioactive peptides determined from this research will help us continue to understand structure-function relationships more broadly for nanoparticle-based drug delivery systems. To avoid the undesirable systemic effects induced by oral administration or subcutaneous injection of immunosuppressants, I have designed a novel polyester hydrogel drug delivery device capable of achieving localized and controllable delivery of thiol-containing immunomodulatory peptides. Glutathione was used as a candidate therapeutic to test this system for which the hydrophilicity of the polymer backbone was modulated to achieve sustained drug release over six to ten days.