(517e) Novel Immunomodulatory Peptide Polymers for Vascularized Composite Allograft Rejection Prevention

Since the first hand transplant was performed nearly two decades ago, the use of vascularized composite allografts (VCA) provides patients who are suffering from devastating tissue loss such as limb amputation or significant facial disfigurement with full functional equivalents greatly improving their quality of life. To prevent VCA rejection, aggressive immunosuppressive strategies are employed for life which limits the patient’s capacity to fight infection and undergo would healing as well as increasing their cancer risk. Unfortunately, even with this approach, approximately 55% of face transplant recipients and as many as 85% of hand transplant recipients experienced acute rejection episodes in the first year post-transplantation.

The goal of our research is to create a novel system capable of facilitating localized immunosuppression through the recruitment and polarization of a variety of immune cells (i.e. macrophages, dendritic cells, and T cells) towards anti-inflammatory and/or tolerogenic phenotypes. Previous research has determined that the hormone-related vasoactive intestinal peptide (VIP) possesses potent pleotropic effects including strong immunomodulatory capacity. Unfortunately, VIP has a half-life of only a few minutes in the body. To enhance the prolonged regional supply of VIP, we have created a novel degradable polyester for which VIP can be readily incorporated into the polymer backbone. Our data demonstrate that directed delivery of VIP have an immunosuppressive effect on multiple types of antigen presenting cells as well as enhance CCL22 production from dendritic cells. As CCL22 is a chemokine with strong regulatory T cell recruitment capacity, this can complement the localized anti-inflammatory effects to further prevent tissue rejection. Taken together, these results provide considerable evidence that VIP-containing polymers hold tremendous potential for limiting transplant rejection.