Validation of high gradient magnetic field based drug delivery to magnetizable implants under flow.

The drug-eluting stent's increasingly frequent occurrence late stage thrombosis have created a need for new strategies for intervention in coronary artery disease. This paper demonstrates further development of our minimally invasive, targeted drug delivery system that uses induced magnetism to administer repeatable and patient specific dosages of therapeutic agents to specific sites in the human body. Our first aim is the use of magnetizable stents for the prevention and treatment of coronary restenosis; however, future applications include the targeting of tumors, vascular defects, and other localized pathologies. Future doses can be administered to the same site by intravenous injection. This implant-based drug delivery system functions by placement of a weakly magnetizable stent or implant at precise locations in the cardiovascular system, followed by the delivery of magnetically susceptible drug carriers. The stents are capable of applying high local magnetic field gradients within the body, while only exposing the body to a modest external field. The local gradients created within the blood vessel create the forces needed to attract and hold drug-containing magnetic nanoparticles at the implant site. Once these particles are captured, they are capable of delivering therapeutic agents such as antineoplastics, radioactivity, or biological cells.

Regulation of axon guidance and extension by three-dimensional constraints.

Axons in vivo are guided by molecular signals acting as attractants and repellents, and possibly by physical constraints encountered in the extracellular environment. We analyzed the ability of primary sensory axons to extend and undergo guidance in three-dimensional (3-D) environments generated using photolithography. Confinement of neurons in fully enclosed square chambers decreased the percentage of neurons establishing axons as a function of chamber width. However, the ability to extend an axon in one or more directions allowed axons to form and extend similarly to those on two-dimensional (2-D) substrata. Live imaging of growth cones interacting with the walls of chambers or corridors revealed that growth cones respond to contact with a 3-D constraint by decreasing surface area, and circumvent constraints by repeated sampling of the constraint until an unobstructed path is encountered. Analysis of the ability of axons to turn around corners in corridors revealed that the angle of the corner and corridor width determined the frequency of turning. Finally, we show that the length of axons can be controlled through the use of 3-D constraints. These data demonstrate that 3-D constraints can be used to guide axons, and control the extent of axon formation and the length of axons.