Browsing by Subject "Microdialysis"

The success of implanted medical devices, such as biosensors, is dependent on the immune reaction to the surface of the implanted material. This immune reaction, termed the foreign body reaction, is potentially affected by the physical and chemical properties of the implanted material. Macrophages interact with the surface of the implanted material and secrete intercellular signals, including cytokines and growth factors, which direct the actions of immune cells in the surrounding tissue. The type and quantity of cytokines and growth factors produced by macrophages at an implant surface could be an indicator of the outcome of the foreign body reaction.

This study investigated the effect of the surface chemistry of an implanted device on the production of cytokines and growth factors. First, microdialysis sampling was characterized as a technique for collecting cytokines and growth factors from the tissue surrounding an implant. Based on this characterization, it was determined that a direct sampling method would be more suitable than microdialysis sampling for determining accurate tissue concentrations of cytokines and growth factors. Second, an in vitro model was developed and utilized to assess cytokine and growth factor production from monocyte/macrophage cultures seeded onto commonly implanted polymeric biomaterials with varying surface chemistries. The materials included in this study were polyethylene (PE), polyurethane (PU), polymethyl methacrylate (PMMA), expanded polytetrafluoroethylene (ePTFE), and a cytotoxic organo-tin polyvinyl chloride (ot-PVC) as a positive control. From this in vitro model, it was determined that the varying surface chemistries of these non-toxic materials, excluding ot-PVC, did not significantly affect the types and quantities of cytokines and growth factors produced. Finally, an in vivo model for evaluating the cytokine and growth factor response to an implanted biomaterial was utilized for comparison with the in vitro findings. In this model, biomaterials were implanted subcutaneously within the lumen of a stainless steel mesh cage. The mesh cage served to create a "pocket" where wound exudate fluid collected within the cage, surrounding the implanted biomaterial. The materials included in this study were PE, PU, and ot-PVC. Cytokines and growth factors produced at the material surface were sampled directly from the exudate fluid. The results from this in vivo study indicate that cytokine and growth factor production were not significantly impacted by the varying surface chemistries of the implanted biomaterials. The in vivo data support the findings from the in vitro model, suggesting that the foreign body reaction proceeds in a similar fashion for each of these non-cytotoxic, polymeric biomaterials with varying surface chemistries.

The catecholamines - norepinephrine and dopamine- are released into cortex from subcortical nuclei. It is classically assumed, for example, that dopamine receptors in cortex bind molecules released by dopaminergic axons. In the case of cortex, those axons would be the ascending fibers of the ventral tegmental area (VTA). Interestingly, dopamine receptors are found in all layers of primary visual cortex (V1), but the innervation from the VTA is mostly restricted to layers 1 and 6. This anatomical mismatch raises the question as to whether or not dopamine from the VTA is the primary ligand for dopamine receptors in V1. An alternative possibility is that the locus coeruleus (LC) co-releases dopamine and norepinephrine into V1. LC axons innervate all layers of V1 and are thus anatomically positioned to provide a ligand to activate dopamine receptors. Another possibility is that dopamine from VTA axons passively diffuses to the middle layers of V1 from layers 1 and 6, and a third possibility is that norepinephrine is binding to these middle layer dopamine receptors. I will present results from a series of studies that address these three possibilities in which I find that activation of the LC can elicit release of both catecholamines into V1 in a manner that depends on experimental parameters such as the intensity and frequency of electrical stimulation of the LC. The data suggests that the LC co-releases dopamine with norepinephrine in a state-dependent manner.