Immature dendritic cells (iDCs) were derived from human peripheral blood monocytes, and treated with 75:25 poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) or film to assess the resultant dendritic cell (DC) maturation as compared to positive control of lipopolysaccharide (LPS) treatment for DC maturation or negative control of untreated iDCs. The effect of PLGA contact on DC maturation was examined as one possible explanation for the PLGA adjuvant effect we have observed in the enhancement of an immune response to codelivered model antigen, as adjuvants act through the maturation of DCs. Culturing iDCs with PLGA MPs or PLGA film resulted in morphology similar to that of LPS-matured DCs and the association, or possible internalization, of PLGA MPs. Furthermore, biomaterial-treated iDCs demonstrated an increase in MHC class II and costimulatory molecule expression compared to iDCs but to a lower level than that of LPS-matured DCs. Direct iDC contact with PLGA MPs was necessary for maturation. Immature DCs exposed to PLGA MPs were stimulatory of allogeneic T-cell proliferation, whereas cells exposed to PLGA film were not. Further, PLGA MPs supported a moderate delayed type hypersensitivity reaction in mice indicative of in vivo DC maturation. Taken together, these results suggest that PLGA is a DC maturation stimulus and that the form of the biomaterial may influence the extent of DC maturation.
"Smart" materialsmaterials that respond to a stimulus or their environment to produce a dynamic and reversible change in critical propertieshave enabled progress in many areas, including display technologies, drug delivery, and self-healing materials for coating applications, among others. Many of the current examples of smart materials are biomimetic, since nature employs and depends on dynamic and rapid switching for critical functions such as vision, camouflage, and ion channel regulation. Despite progress in designing smart materials and surfaces, much work is still needed in this area to increase their implementation in useful applications. In this Perspective, the challenges and outlook in this field are highlighted, including the work of Balazs and co-workers found in this issue of ACS Nano.
Biodegradable, compositionally anisotropic microparticles with two distinct compartments that exhibit controlled shapes and sizes are fabricated. These multifunctional particles are prepared by electrohydrodynamic co-jetting of poly(lactide-co-glycolide) polymer solutions. By varying different solution and process parameters, namely, concentration and flow rate, a variety of non-equilibrium bicompartmental shapes, such as discoid and rod-shaped microparticles are produced in high yields. Optimization of jetting parameters, combined with filtration, results in near-perfect, bicompartmental spherical particles in the size range of 3-5 microm. Simultaneous control over anisotropy, size, shape, and surface structure provides an opportunity to create truly multifunctional microparticles for a variety of biological applications, such as drug delivery, diagnostic assays, and theranostics.
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