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Here, we report the preparation of carbon dots (CDs) and doping with different elements namely boron, nitrogen and phosphorous using facile single step hydrothermal method. We used biopolymers as the source material for CDs synthesis. The prepared carbon dots and elements (B, N and P) doped carbon dots’ physicochemical properties are investigated using different analytical techniques. Several analytical characteristics such as Uv-visible spectroscopy, fluorescent spectroscopy and transmission electron microscopy confirm the doping of element into carbon dots. From DLS analysis it was found that the prepared carbon dots are range from 3-9 nm. Excitation dependent fluorescence with high quantum yields for B and N doped CDs showed 47% and 44%, respectively. The doped CDs impact on cell viability was investigated against neuronal PC12 cells. Interestingly, the prepared carbon dots did not affect the differentiation process of neuronal cells. Hence, the highly fluorescent CDs can be served as excellent materials for neural tissue engineering as well as biomedical engineering applications.

Directing neuronal migration and growth has an important impact on potential post traumatic therapies. Magnetic manipulation is an advantageous method for remotely guiding cells. In the present study, we have generated highly localized magnetic fields with controllable magnetic flux densities to manipulate neuron-like cell migration and organization at the microscale level. We designed and fabricated a unique miniaturized magnetic device composed of an array of rectangular ferromagnetic bars made of permalloy (Ni80Fe20), sputter-deposited onto glass substrates. The asymmetric shape of the magnets enables one to design a magnetic landscape with high flux densities at the poles. Iron oxide nanoparticles were introduced into PC12 cells, making the cells magnetically sensitive. First, we manipulated the cells by applying an external magnetic field. The magnetic force was strong enough to direct PC12 cell migration in culture. Based on time lapse observations, we analysed the movement of the cells and estimated the amount of MNPs per cell. We plated the uploaded cells on the micro-patterned magnetic device. The cells migrated towards the high magnetic flux zones and aggregated at the edges of the patterned magnets, corroborating that the cells with magnetic nanoparticles are indeed affected by the micro-magnets and attracted to the bars' magnetic poles. Our study presents an emerging method for the generation of pre-programmed magnetic micro-'hot spots' to locate and direct cellular growth, setting the stage for implanted magnetic devices.

Growth factors play an important role in nerve regeneration and repair. An attractive drug delivery strategy, termed &ldquo, magnetic targeting&rdquo, aims to enhance therapeutic efficiency by directing magnetic drug carriers specifically to selected cell populations that are suitable for the nervous tissues. Here, we covalently conjugated nerve growth factor to iron oxide nanoparticles (NGF-MNPs) and used controlled magnetic fields to deliver the NGF&ndash, MNP complexes to target sites. In order to actuate the magnetic fields a modular magnetic device was designed and fabricated. PC12 cells that were plated homogenously in culture were differentiated selectively only in targeted sites out of the entire dish, restricted to areas above the magnetic &ldquo, hot spots&rdquo, To examine the ability to guide the NGF-MNPs towards specific targets in vivo, we examined two model systems. First, we injected and directed magnetic carriers within the sciatic nerve. Second, we injected the MNPs intravenously and showed a significant accumulation of MNPs in mouse retina while using an external magnet that was placed next to one of the eyes. We propose a novel approach to deliver drugs selectively to injured sites, thus, to promote an effective repair with minimal systemic side effects, overcoming current challenges in regenerative therapeutics.

Nerve growth strongly relies on multiple chemical and physical signals throughout development and regeneration. Currently, a cure for injured neuronal tissue is an unmet need. Recent advances in fabrication technologies and materials led to the development of synthetic interfaces for neurons. Such engineered platforms that come in 2D and 3D forms can mimic the native extracellular environment and create a deeper understanding of neuronal growth mechanisms, and ultimately advance the development of potential therapies for neuronal regeneration. This progress report aims to present a comprehensive discussion of this field, focusing on physical feature design and fabrication with additional information about considerations of chemical modifications. We review studies of platforms generated with a range of topographies, from micro-scale features down to topographical elements at the nanoscale that demonstrate effective interactions with neuronal cells. Fabrication methods are discussed as well as their biological outcomes. This report highlights the interplay between neuronal systems and the important roles played by topography on neuronal differentiation, outgrowth, and development. The influence of substrate structures on different neuronal cells and parameters including cell fate, outgrowth, intracellular remodeling, gene expression and activity is discussed. Matching these effects to specific needs may lead to the emergence of clinical solutions for patients suffering from neuronal injuries or brain-machine interface (BMI) applications.

The search for regenerative agents that promote neuronal differentiation and repair is of great importance. Nerve growth factor (NGF) which is an essential contributor to neuronal differentiation has shown high pharmacological potential for the treatment of central neurodegenerative diseases such as Alzheimer's and Parkinson's. However, growth factors undergo rapid degradation, leading to a short biological half-life. In our study, we describe a new nano-based approach to enhance the NGF activity resulting in promoted neuronal differentiation. We covalently conjugated NGF to iron oxide nanoparticles (NGF-NPs) and studied the effect of the novel complex on the differentiation of PC12 cells. We found that the NGF-NP treatment, at the same concentration as free NGF, significantly promoted neurite outgrowth and increased the complexity of the neuronal branching trees. Examination of neuronal differentiation gene markers demonstrated higher levels of expression in PC12 cells treated with the conjugated factor. By manipulating the NGF specific receptor, TrkA, we have demonstrated that NGF-NPs induce cell differentiation via the regular pathway. Importantly, we have shown that NGF-NPs undergo slower degradation than free NGF, extending their half-life and increasing NGF availability. Even a low concentration of conjugated NGF treatment has led to an effective response. We propose the use of the NGF-NP complex which has magnetic characteristics, also as a useful method to enhance NGF efficiency and activity, thus, paving the way for substantial neuronal repair therapeutics.

Background The ability to direct and manipulate neuronal cells has important potential in therapeutics and neural network studies. An emerging approach for remotely guiding cells is by incorporating magnetic nanoparticles (MNPs) into cells and transferring the cells into magnetic sensitive units. Recent developments offer exciting possibilities of magnetic manipulations of MNPs-loaded cells by external magnetic fields. In the present study, we evaluated and characterized uptake properties for optimal loading of cells by MNPs. We examined the interactions between MNPs of different cores and coatings, with primary neurons and neuron-like cells. Results We found that uncoated-maghemite iron oxide nanoparticles maximally interact and penetrate into cells with no cytotoxic effect. We observed that the cellular uptake of the MNPs depends on the time of incubation and the concentration of nanoparticles in the medium. The morphology patterns of the neuronal cells were not affected by MNPs uptake and neurons remained electrically active. We theoretically modeled magnetic fluxes and demonstrated experimentally the response of MNP-loaded cells to the magnetic fields affecting cell motility. Furthermore, we successfully directed neurite growth orientation along regeneration. Conclusions Applying mechanical forces via magnetic mediators is a useful approach for biomedical applications. We have examined several types of MNPs and studied the uptake behavior optimized for magnetic neuronal manipulations. Electronic supplementary material The online version of this article (doi:10.1186/s12951-016-0190-0) contains supplementary material, which is available to authorized users.