Intraoperatively defined tumor characteristics played a critical role in identifying the subset of patients with an increased risk of postoperative deficits. By selectively pursuing an NTR rather than a GTR, neurological morbidity was reduced significantly without significantly increasing the rate of tumor recurrence.
An IV general anesthetic technique using remifentanil and propofol is an effective method allowing for reliable emergence for intraoperative awake functional brain mapping during craniotomy.
This work demonstrates the ability of sol-gel derived materials to support the differentiation of neuronal cells, and investigates the physiochemical interactions between the surface and extracellular matrix proteins as a mediator of the effects of surface features on differentiation. We have applied fluorescence resonance energy transfer (FRET) spectroscopy to study the conformational changes of human serum fibronectin, a critical extracellular cell adhesion protein, after adsorption onto native and poly-L-lysine doped sol-gel derived silica thin films and bulk materials. The global conformation of fibronectin varied dramatically between native and organically modified materials and most interestingly between thin films and bulk materials of the same chemistry. A comparison of the surface topography of thin films and bulk materials by atomic force microscopy reveals that films of native silica have surface features less than the AFM tip size (,25 nm) while bulk materials of the same precursor chemistry have features ranging from 50-100 nm in size. Fibronectin assumed an inactive, globular, solution-like state on the larger feature size bulk gels and an active, fully extended fibrillar-like state on the smaller feature size films. Neither native nor PLL-doped bulk materials could support cell growth or neuronal differentiation of PC12 cells, in stark contrast to the thin films, which supported a robust neuronal phenotype. Morphological analysis and expression levels of the neuronal proteins b-tubulin and neurofilament, in addition to the FRET data, indicate that the effects of surface chemistry on fibronectin conformation, cellular adhesion, and differentiation are dependent upon the surface topography.
Peptide-functionalized thin films exhibit significant potential for integration into implantable devices and cell-based technologies. A new type of neuroactive peptide-modified silica was developed using sol-gel reaction chemistry to produce thin films from four different peptide silane precursors. Peptide silanes containing binding sequences from laminin (YIGSR and KDI), fibronectin (RGD), and EGF repeats from laminin and tenascin (NID) were produced using standard solid-state FMOC peptide synthesis conditions and the covalent attachment of 39-(aminopropyl)trimethoxysilane (APTMS), using carbonyldiimadazole (CDI) as a linking molecule. Precursor formation was confirmed with MALDI-MS. Thin films were produced by dip-coating using the peptide precursors combined with hydrolyzed tetramethoxysilane. Atomic force microscopy indicated that the surface topography was not affected by low concentrations of peptide precursor (0.0025 mol%), but higher concentrations of peptide precursor (0.01 mol%) resulted in features that were 50-75 nm in height. The height features observed were consistent in size with previously determined topographical morphology supportive of neuronal cell lines. The surfaces were biologically active and modulated the phenotype of the embryonic carcinoma stem cell line, P19. Combinations of the peptide silanes resulted in altered cell types after retinoic acid treatment. More neurons were observed on RGD/YIGSR and RGD/YIGSR/NID surfaces compared to tetramethoxysilane (TMOS) controls. More supporting cells were observed compared to collagen coated tissue culture plates. In addition, neurites were significantly longer on the peptide ormosils compared to controls. This work demonstrates a novel method for producing biologically active peptide ormosils using peptide-modified precursors.
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