Astrocyte infiltration into injectable collagen-based hydrogels containing FGF-2 to treat spinal cord injury.

Astrocytes can play dual roles in the response to spinal cord injury (SCI) acting as both an inhibitory barrier and a trophic support for growth axons. Therefore, migration of these cells into the defect as opposed to forming a scar at the periphery, may promote axon regeneration through the lesion. However, infiltration requires the conformal filling of the cyst-like lesion, which often forms after SCI, with a biomaterial scaffold encouraging of astrocyte migration. For this application, we investigated injectable collagen-based hydrogels covalently cross-linked with genipin and incorporating fibroblast growth factor-2 (FGF-2) either freely or encapsulated within lipid microtubules (LMTs). An outgrowth assay was used to evaluate in vitro the number of primary rat astrocytes infiltrating into the collagen gels and the distance to which they infiltrated. The presence of FGF-2 within the encapsulating gel significantly increased the number of astrocytes within the gel, their penetration distance into the gel, and caused them to move out in a chain-like pattern, compared to control gels without FGF-2. Genipin cross-linking of the collagen gel decreased the number of infiltrating astrocytes, compared to the non-cross-linked control gel; however, incorporation of FGF-2-containing LMTs within genipin-cross-linked gels restored the astrocyte infiltration to levels approaching non-cross-linked gels incorporating FGF-2. Overall, injectable collagen-genipin hydrogels containing FGF-2-containing LMTs are a promising candidate for the treatment for SCI through the attraction of astrocytes into the graft.

Zero-order controlled release of ciprofloxacin-HCl from a reservoir-based, bioresorbable and elastomeric device.

A reservoir-based device constructed of a completely biodegradable elastomer can enable several new implantation and insertion options for localized drug therapy, particularly in the case of urological therapies. We performed an in vitro performance evaluation of an implantable, bio-resorbable device that supplies short-term controlled release of ciprofloxacin-HCl (CIP). The proposed device functions through a combination of osmosis and diffusion mechanisms to release CIP for short-term therapies of a few weeks duration. Poly(glycerol-co-sebacic acid) (PGS) was cast in a tubular geometry with solid drug powder packed into its core and a micro-machined release orifice drilled through its wall. Drug release experiments were performed to determine the effective release rate from a single orifice and the range of orifice sizes in which controlled zero-order release was the main form of drug expulsion from the device. It is demonstrated that PGS is sufficiently permeable to water to allow the design of an elementary osmotic pump for drug delivery. Indeed, PGS's water permeability is several orders of magnitude larger than commonly used cellulose acetate for elementary osmotic pumps.

Integration of a surface-directed microfluidic system with an organic electrochemical transistor array for multi-analyte biosensors.

We report the integration of organic electrochemical transistors with a surface-directed microfluidic system. The end product is a chip in which an analyte solution is distributed in four separate measurement reservoirs, each containing a transistor that uses the analyte as an integral part of its device structure. The use of a surface-directed microfluidic system enables the distribution of the analyte solution without the application of external pressure. The use of this chip in the detection of multiple analytes is demonstrated.

All-plastic electrochemical transistor for glucose sensing using a ferrocene mediator.

We demonstrate a glucose sensor based on an organic electrochemical transistor (OECT) in which the channel, source, drain, and gate electrodes are made from the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS). The OECT employs a ferrocene mediator to shuttle electrons between the enzyme glucose oxidase and a PEDOT:PSS gate electrode. The device can be fabricated using a one-layer patterning process and offers glucose detection down to the micromolar range, consistent with levels present in human saliva.

cADPR analogues: effect of an adenosine 2'- or 3'-methoxy group on conformation.

[structure: see text] The 2'-OMe-A (2) and 3'-OMe-A (3) analogues of the calcium release agent cADPR (1) were prepared and their solution structures studied by NMR spectroscopy. Compared to 1, 2 shows a shift in its A ring conformation and changes in its R ring N:S and gammat:gamma+ ratios, while 3 displays a significant change in the conformation of its A ring gamma-bond.