Both solid organ and vascularized composite allotransplants are prone to rejection, an immunological response prompted by the recognition of donor tissue. To prevent this reaction, patients are placed on systemic immunosuppressive drugs. However, these drugs place patients at risk for a variety of toxicities (i.e., infection, nephrotoxicity, etc.). Thus, we have developed local drug delivery systems capable of inducing immunosuppressive effects at the site of the transplant, prolonging graft survival without the need for systemic immunosuppression. 

We have engineered a long-term delivery system for the sinuses called TEMPS (Thermogel, Extended-release Microsphere-based delivery system to the paranasal sinuses). TEMPs consists of controlled release microspheres embedded in a thermoresponsive hydrogel so that the system can be applied as a liquid and conform to the sinonasal epithelium as it gels at body temperature. In addition to developing and characterizing the system, we have evaluated its safety and efficacy in a rabbit model of chronic rhinosinusitis in collaboration with Ear, Nose and Throat Clinicians.  

Periodontal (Perio) disease is an oral health concern that impacts over 64 million individuals in the United States. Perio can be characterized by both a pathogenic infection and an overactive immune response. To combat the immune response, we have engineered a controlled drug delivery system to locally deliver a specific immunological signal which can promote immunosuppression restore immune homeostasis in the oral cavity. Our group has tested this approach in both murine and canine models of periodontal disease in collaboration with dentists in the University of Pittsburgh Dental School.  

Myocardial infarction (MI, heart attack) is one of the most prevalent cardiac events in the United States. Current therapies do not adequately treat the underlying dysregulated processes that follow heart attacks, including reperfusion injury and pathogeneic remodeling. Therefore, we are working to improve the way that they heart responds MI by enhancing the tissue reparation process. To achieve this, we are focused on developing local delivery strategies that manipulate the immunological microenvironment and promote tissue restoration.  

Allergic contact dermatitis is a destructive T-cell-mediated inflammation of the skin, resulting from repeated contact with allergens (i.e., nickel, poison ivy). Aside from avoiding known allergens when possible, current treatments involve non-specific anti-inflammatories that locally suppress cutaneous inflammation, but fail to address the underlying immune imbalance. Our studies aim to induce tolerance to chemical allergens or protein antigens by engineering local skin or lymph node microenvironments. To that end, we deliver antigens and tolerance-inducing factors to the skin or skin draining lymph nodes, using dissolvable microneedle arrays (MNAs) or sustained release microparticles, respectively. In addition to evaluating these systems in various murine models, translational studies with human skin explants are designed to enable translation of these therapeutic strategies to clinical trials.