Following implantation, medical devices often trigger different extent of foreign body reactions. Using mice subcutaneous implantation model, we have studied the processes governing foreign body reactions to hydrogel microparticles. By determining a broad panel of cell surface markers, we have accidentally discovered that migratory stem cells are accumulated in the fibrotic capsule or in the microparticle implants. Since the recruitment of stem cells coincides with the immigration of inflammatory cells, we have assumed that stem cells are actively recruited by inflammatory signals released by inflammatory cells associated with biomaterial implants. Thus, the numbers of recruited stem cells would be significantly reduced if the extent of foreign body reactions is diminished. To test this hypothesis, we used poly-N-isopropylacrylamide (PNIPAM) microparticles which some of them were loaded with different inflammatory agents. Following implantation, the extent of biomaterial-mediated inflammatory responses and stem cell recruitment were assessed using immunohistological analyses. In this study, we have emphasized on anti-histamine blockers and anti-inflammatory steroid for the following reasons. First, we recently found that andhistamin blockers (H1 blocker - pyrilamine; H2 blocker - famotidine) effectively reduced the adherent phagocyte on both intraperitoneal and subcutaneously implanted biomaterials. Second, many previous studies have shown that the release of anti-inflammatory drugs significantly diminish the accumulation of inflammatory cells on implant surfaces.
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