Nano LIFE

Stromal cell-derived growth factor-1 (SDF1) is a chemokine that is over-expressed at sites of injury and is believed to play an important role in wound repair. At the cellular level, SDF1 regulates the mobilization and trafficking of endothelial progenitors that originate in the bone marrow and functionally contribute to neovascularization and angiogenesis in the wound. Consequently, SDF1 is a potentially interesting therapeutic with the potential to enhance these processes in acute and chronic injuries that otherwise tend to heal poorly, such as spinal cord injury, stroke, myocardial infarction, diabetic skin wounds and acute burns. However, the therapeutic usefulness of SDF1, as many other similar peptide-based growth factors and chemokines, is severely limited due to its short in vivo half-life, as it is rapidly degraded by proteases, which are typically very abundant at the wound site. Several studies have reported methodologies to increase SDF1 in vivo stability by mutating the protease cleavage sites of the molecule. Another approach has been to incorporate the chemokine into biomaterials that shield it from degradation. Yet another approach would be to develop a system that is inherently stable and could be combined with these aforementioned strategies. For example, self-assembled nanoparticles could shield SDF1 (or one of its forms engineered to be more resistant to proteolysis) from proteolysis and then be incorporated into suitable biomaterials. Nanotechnology-based delivery systems have however been used to a very limited extent for SDF1. This paper aims to provide a summary of the various stabilization and delivery methods available for SDF1, some of which have been already used, as well as others that have been used with other bioactive peptides, but would be potentially applicable to SDF1.

Carbon dots (Cdots) have been widely applied in labeling cellular or subcellular targets with high resolution due to their small sizes and benign biocompatibility. However, their use for in vivo application suffered from the rapid renal clearance due to their tiny size (c.a. $<\sim$6nm in diameter). To overcome the drawback, we herein report a sonication assisted method for the preparation of Cdots clusters with tunable sizes. Pluronic F127 was used as the carrier to form the clusters and the feeding ratio of the Cdots to F127 was varied in order to tune the sizes of clusters. The clusters were also successfully demonstrated in cell imaging applications with high brightness. Together with their low cytotoxicity, the clusters are potential for bioimaging applications. Hence, this work provides a convenient engineering strategy to prepare Cdots clusters with tunable sizes for bioimaging applications.

The manipulation of biological substrates is becoming more popular route toward generating novel computing devices. Physarum polycephalum is used as a model organism in biocomputing because it can create “wires” for use in hybrid circuits; programmable growth by manipulation through external stimuli and the ability withstanding a current and its tolerance to hybridization with a variety of nano/microparticles. Lettuce seedlings have also had previous interest invested in them for generating plant wires, although currently there is little information as to their suitability for such applications. In this study both P. polycephalum and Lettuce seedlings were hybridized with gold nanoparticles — functionalized and unfunctionalized — to explore their uptake, toxicological effects and, crucially, any alterations in electrical properties they bestow upon the organisms. Using various microscopy techniques it was shown that P. polycephalum and lettuce seedlings are able to internalize nanoparticles and assemble them in vivo, however some toxicological effects were observed. The electrical resistance of both lettuce seedlings and P. polycephalum was found to decrease, the most significant reduction being with lettuce seedlings whose resistance reduced from 3M$\mathrm{\Omega }$s to 0.5M$\mathrm{\Omega }$s. We conclude that gold is a suitable nanomaterial for biohybridization specifically in creating conductive pathways for more efficient biological wires in self-growing hybrid circuitry.

In this paper, we have developed self-assembled nanoscale assemblies that were prepared by conjugating furan-2-carboxylic acid-3-aminopropyl amide with the short peptide sequence Gly-His (abbreviated Gly-His-FCAP). To mimic the extracellular matrix of mammalian fibroblasts and keratinocytes, the assemblies were then conjugated with Type I collagen. We then integrated the collagen bound Gly-His-FCAP assemblies with a short peptide sequence derived from salamander skin into the nanoscale assemblies for the first time to impart regenerative and wound healing properties to the composites. The antioxidant, antimicrobial and biodegradable properties were examined and results indicate that the nanocomposites displayed antioxidant properties as displayed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The biodegradability was found to be gradual. The nanocomposites were also found to inhibit the growth of the fungus Rhizopus sporangia over an 18h growth period. As proof of concept, to demonstrate the development of three-dimensional (3D) engineered skin in vitro, 3D printed PLA scaffolds of 2.5mm thickness were submerged in media containing nanocomposites and co-cultures of dermal fibroblasts with epidermal keratinocytes mimicking three dimensional skin substitute was examined. Our results indicated that the nanocomposites adhered to and supported cell proliferation and mimicked the components of skin and may have potential applications in skin tissue regeneration.

Cellular replacement therapies for myelin disorders require large numbers of cells and relatively mature oligodendrocytes. Oligodendrocyte differentiation from a pluripotent state often involves long protracted protocols. In this study, we investigated the effect that activation of peroxisome proliferator activator receptors (PPAR) alpha, delta and gamma would have on oligodendrocyte differentiation of mouse embryonic stem (mES) cells. Using a two-dimensional (2D) differentiation platform, oligodendrocyte differentiation stalled at the immature oligodendrocyte stage, i.e., CNPase positive cells. When PPAR agonists for alpha, delta and gamma were added, oligodendrocyte differentiation was accelerated with higher numbers of O1 and CNPase positive cells being detected. PPAR agonist addition also resulted in phenotypic changes with alpha agonist addition resulting in an increase in process length compared to control with some increased secondary branching, delta agonist addition resulted in longer primary process length, and gamma agonist addition resulted in a larger cell soma and more tertiary branching patterns. Placing mES cells into a three-dimensional (3D) alginate nanoporous microcapsule environment, we were able to further mature cells to a myelin basic protein (MBP) expressing stage. The exposure of cells to PPAR agonists within the alginate microcapsules resulted in accelerated maturation with PPAR delta in particular showing a sustained high expression of MBP. The combined effect of PPAR activation in a 3D environment demonstrates a relatively simple and efficient method to differentiate mES cells into mature oligodendrocytes.

Plasmonic gold nanostructures offer a promising route to improving the solar energy conversion efficiency of semiconductors. This paper reports that the presence of gold nanoparticles (NPs) on the surface of TiO₂ nanorods leads to an enhanced photocurrent for the photoelectrochemical (PEC) water splitting performance and discusses the origins of this enhancement from the results of various characterization techniques. The results show that plasmon-induced resonant energy transfer is responsible for the light harvesting enhancement at the energies below the band edge of TiO₂. These results may provide a general approach to overcoming the low optical absorption of semiconductor structures, while further reducing the charge recombination losses.