| Modulation of immune-cell responses using biomaterials based cues is an exciting field of research that holds great potential to help solve disorders such as autoimmune diseases, cancer and infections. Medical devices used in numerous applications such as tissue-engineered constructs, combination products (e.g., drug-eluting stents) and therapeutic vaccines are excellent tools for modulating the immune system. Since dendritic cells (DCs) are the key regulators of the immune system, DCs can be targeted to generate a desired immune response. Dendritic cell functions can be altered using several different signals such as adhesion signaling, targeting extracellular/intracellular toll like receptors for activation and mechanical cues. Specifically, we are interested in modulating DC behavior using adhesion cues and delivery of agents that target extracellular and intracellular receptors.;Exogenously generated DCs have been suggested as a potential solution to diseases such as type 1 diabetes (T1D). Ex vivo expansion of cells require isolation from the patient and culturing them on tissue culture treated plates where they come in contact with several different proteins. Adhesion of such cells on different extracellular matrix proteins can modulate cellular responses. While it is well-known that adsorbed proteins on biomaterials modulate inflammatory responses in vivo, modulation of dendritic cells (DCs), a key regulator of immune system, via adhesion-dependent signaling has only been begun to be characterized. Currently, DC-based immunotherapy approaches for diseases such as cancer and autoimmune diseases like type-I diabetes rely on ex vivo culture and expansion of patient-derived DCs onto tissue culture-treated polystyrene plates. The adhesive substrate provided for DCs in this ex vivo approach is typically tissue culture-treated polystyrene presenting serum proteins adsorbed from the culture media. We therefore chose to examine serum-coated tissue culture-treated polystyrene as a relevant benchmark to compare the effect of adhesion-dependent modulation of DC function when cultured on several of the extracellular matrix proteins. Furthermore, DCs isolated from non-obese diabetic mice and its background control of wild type mice were cultured on the extracellular matrix proteins and compared for optimal protein substrate for generating DC based vaccines. In addition to modulating DCs ex vivo, DCs can be targeted in vivo using particle-based vaccines. Currently there are scores of known antigenic epitopes and adjuvants, and numerous synthetic delivery systems accessible for formulation of vaccines. However, the lack of an efficient means to test immune cell responses to the abundant combinations available represents a significant blockade on the development of new vaccines. In order to overcome this barrier, we report fabrication of a new class of microarray consisting of antigen/adjuvant-loadable poly(D,L lactide-co-glycolide) microparticles (PLGA MPs), identified as a promising carrier for immunotherapeutics, that are cultured with DCs. Furthermore, a technique was generated to manufacture scores of particle-based vaccines in a highthroughput manner. The intention is to utilize this high-throughput platform to optimize particle-based vaccines designed to target DCs in vivo for immune system-related disorders, such as autoimmune diseases, cancer and infection. |
