(251c) Development of a Multicompartment Immunocompetent Skin Tissue Model Using 3D Freeform Fabrication

Skin forms a first line of defense against pathogens, environmental insults and trauma. In addition to being a formidable physical barrier, skin hosts a highly sophisticated and robust network of immune surveillance agents. The high accessibility of skin and its inherent immunological activity make it an attractive interface for vaccination. Transdermal vaccination is especially advantageous since it can induce cellular (cytotoxic T cell based) immunity as well as humoral (B cell or antibody based) immunity to ensure adequate protection against an infection. Contemporary literature in skin immunobiology has highlighted key immune components and their roles in the cutaneous immune network. To develop effective transdermal immunotherapeutics, a physiologically relevant, multi-compartmental, integrated immune model of the skin is needed. This study describes the design of an in vitro, multi-compartmental, three-dimensional, Human Immunocompetent Skin Tissue Experimental Model (HISTEM) that adequately captures the innate immune response in the dermal/epidermal compartment as well as the adaptive immune response in the skin draining lymph nodes. A novel cell-printing technology called three-dimensional free form fabrication (3DFFF) is employed for the design of HISTEM. 3DFFF is a powerful and flexible technology that allows printing of multi-cellular, multi-layer skin tissue structures in a high-throughput manner. HISTEM has been tested for its ability to initiate innate and adaptive immune responses when challenged with known irritants, allergens and antigens. The long term goal of this study is to build upon the successful development of HISTEM, and focus on rational design of novel transdermal vaccines and immunomodulators. Skin-patch based transcutaneous vaccines are expected to make a significant impact on mass vaccination programs as well as limit the accidental spread of infections among healthcare providers through needle-sticks. Beyond use as prophylactics against systemic infections, transdermal immunotherapeutics have the potential as novel interventions in genetic and acquired immunological disorders of the skin, cutaneous malignancies and immunosuppressive therapies for patients receiving skin transplants.