A cell delivery strategy was investigated that was hypothesized to enable magnetic targeting of endothelial cells to the steel surfaces of intraarterial stents because of the following mechanisms: (i) preloading cells with biodegradable polymeric superparamagnetic nanoparticles (MNPs), thereby rendering the cells magnetically responsive; and (ii) the induction of both magnetic field gradients around the wires of a steel stent and magnetic moments within MNPs because of a uniform external magnetic field, thereby targeting MNP-laden cells to the stent wires. In vitro studies demonstrated that MNP-loaded bovine aortic endothelial cells (BAECs) could be magnetically targeted to steel stent wires. In vivo MNP-loaded BAECs transduced with adenoviruses expressing luciferase (Luc) were targeted to stents deployed in rat carotid arteries in the presence of a uniform magnetic field with significantly greater Luc expression, detected by in vivo optical imaging, than nonmagnetic controls.cell therapy ͉ gene therapy ͉ local delivery ͉ nanotechnology C ell therapy represents a forefront approach with great promise. In particular, reendothelization of diseased or injured arteries is a goal of endothelial-related cell therapies (1, 2). However, there is a paucity of delivery strategies for localizing cell therapy to target sites (1, 2). The present studies report an approach for delivering endothelial cells to intravascular steel stents. Balloon-deployable stents are now the treatment of choice for vasoocclusive disease. Advanced stent designs with drug-eluting capabilities have resulted in a paradigm shift in the care of coronary disease (3-6). However, the lack of reendothelization (1, 2) after stent angioplasty remains an unsolved problem (3-6). Stents are commonly composed of steel alloys, such as the medical-grade stainless-steel 316L, which exhibits a minimal response to external magnetic fields. However, we hypothesized that by using a more magnetically responsive alloy, such as a 304-grade stainless steel, instead of 316L, it would be possible to locally deliver genetically modified endothelial cells to stent surfaces by using magnetic gradient-related mechanisms.Previous investigations of magnetically targeted cell-delivery systems, which have all exclusively used locally applied magnets, rather than uniform magnetic fields, have been hampered by a number of factors. These studies by others (7-9) have used nonbiodegradable magnetic nanoparticles that cannot be removed from the tissue after delivery. More fundamentally, these previous studies used magnetic field sources in a suboptimal manner. Thus, prior work has been limited to using a single source of magnetic field, in which either a locally applied permanent magnet (7,8) or a ferromagnetic medical implant (9) was used to implement the magnetic capture system. Such sources can be designed to increase the magnetizing field of cells loaded with magnetic nanoparticles or the field gradient, but not both, making it impossible to maximize the fraction of captured nanopar...

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Magnetic-based systems utilizing superparamagnetic nanoparticles and a magnetic field gradient to exert a force on these particles have been used in a wide range of biomedical applications. This review is focused on drug targeting applications that require penetration of a cellular barrier as well as strategies to improve the efficacy of targeting in these biomedical applications. Another focus of this review is regenerative applications utilizing tissue engineered scaffolds prepared with the aid of magnetic particles, the use of remote actuation for release of bioactive molecules and magneto–mechanical cell stimulation, cell seeding and cell patterning.

One of the major challenges in engineering thick, complex tissues such as cardiac muscle, is the need to pre-vascularize the engineered tissue in vitro to enable its efficient integration with host tissue upon implantation. Herein, we explored new magnetic alginate composite scaffolds to provide means of physical stimulation to cells. Magnetite-impregnated alginate scaffolds seeded with aortic endothelial cells stimulated during the first 7 days out of a total 14 day experimental course showed significantly elevated metabolic activity during the stimulation period. Expression of proliferating cell nuclear antigen (PCNA) indicated that magnetically stimulated cells had a lower proliferation index as compared to the non-stimulated cells. This suggests that the elevated metabolic activity could instead be related to cell migration and re-organization. Immunostaining and confocal microscopy analyses supported this observation showing that on day 14 in magnetically stimulated scaffolds without supplementation of any growth factors, cellular vessel-like (loop) structures, known as indicators of vasculogenesis and angiogenesis were formed as compared to cell sheets or aggregates observed in the non-stimulated (control) scaffolds. This work is the first step in our understanding of how to accurately control cellular organization to form tissue engineered constructs, which together with additional molecular signals could lead to a creation of an efficient pre-vascularized tissue construct with potential applicability for transplantation.