The development of efficient contrast agents for cell labelling coupled with powerful medical imaging techniques is of great interest for monitoring cell trafficking with potential clinical applications such as organ repair and regenerative medicine. In this paper, functionalised multi-walled carbon nanotubes (MWNTs) were engineered for cell labelling in T1-weighted MRI applications. These sophisticated constructs were covalently functionalised with the gadolinium (Gd) chelating agent, diethylene triamine pentaacetic acid (DTPA), enabling tight attachment of Gd atoms onto the nanotube surface. The resulting Gd-labelled MWNTs were found to be stable over 2weeks in water and mouse serum and high payload of Gd atoms could be loaded onto the nanotubes. The r1 relaxivity of the Gd-MWNTs was a 3-fold higher than of the clinically approved T1 contrast agent Magnevist at a magnetic field strength of 7T. The contrast efficiency, expressed as the r1 relaxivity, of the Gd-MWNTs in Human Umbilical Vein Endothelial cells (HUVEC) was investigated at 7T and was found to be around 6.6mM−1s−1. There was no reduction of the contrast efficiency after internalisation in HUVECs, which was imparted to the ability of carbon nanotubes to translocate the cell membrane.

The front cover illustrates the in vivo imaging and controlled swimming of a swarm of microrobots in deep tissue, which is described in detail by K. Kostarelos, B. J. Nelson, and co-workers on page 2981. These microrobots, called artificial bacterial flagella (ABFs), are similar in size and geometry to bacterial flagella, and are capable of 3D navigation in fluids under low-strength rotating magnetic fields (<10 mT). They show potential applications in biomedicine such as targeted therapy.

In vivo imaging and actuation of a swarm of magnetic helical microswimmers by external magnetic fields (less than 10 mT) in deep tissue is demonstrated for the first time. This constitutes a major milestone in the field, yielding a generation of micrometer-scale transporters with numerous applications in biomedicine including synthetic biology, assisted fertilization, and drug/gene delivery.

Stimuli-responsive biomaterials have attracted significant attention in the field of polymeric implants designed as active scaffolds for on-demand drug delivery. Conventional porous scaffolds suffer from drawbacks such as molecular diffusion and material degradation, allowing in most cases only a zero-order drug release profile. The possibility of using external stimulation to trigger drug release is particularly enticing. In this paper, the fabrication of previously unreported graphene hydrogel hybrid electro-active scaffolds capable of controlled small molecule release is presented. Pristine ball-milled graphene sheets are incorporated into a three dimensional macroporous hydrogel matrix to obtain hybrid gels with enhanced mechanical, electrical, and thermal properties. These electroactive scaffolds demonstrate controlled drug release in a pulsatile fashion upon the ON/OFF application of low electrical voltages, at low graphene concentrations (0.2 mg mL(-1) ) and by maintaining their structural integrity. Moreover, the in vivo performance of these electroactive scaffolds to release drug molecules without any "resistive heating" is demonstrated. In this study, an illustration of how the heat dissipating properties of graphene can provide significant and previously unreported advantages in the design of electroresponsive hydrogels, able to maintain optimal functionality by overcoming adverse effects due to unwanted heating, is offered.

Triggerable drug delivery from polymeric implants offers the possibility to generate remote-controlled drug release profiles that may overcome the deficiencies of conventional administration routes (intravenous injections and oral administration) including the toxicity due to overdose and systemic administration. An electro-responsive delivery system was engineered to deliver drug molecules in a pulsatile manner, controlled by the on/off application of electric voltage. Pristine multi-walled carbon nanotubes (pMWNTs) were incorporated into a polymethacrylic acid (PMAA)-based hydrogel matrix by in situ radical polymerisation. The effect of pMWNTs and cross-linker concentration on the electrical and mechanical properties of the hydrogel hybrids was thoroughly investigated. The incorporation of pMWNTs into the polymeric network improved the electrical properties of the hydrogel hybrids and drug release from the gels was significantly enhanced at high pMWNT concentrations, reaching 70% of the loaded dose after two short electrical stimulations. The presence of pMWNTs within the hydrogel matrix affected however the mechanical properties of the hydrogel by decreasing the pore size and therefore the swelling/de-swelling of the gels. The damage to the hybrid gel surfaces after electrical stimulation and the loss of the pulsatile release profile at high cross-linker concentrations suggested that the mechanism of drug release involved a compressing effect and intensified the stress on the polymeric network as a result of the electrical properties of pMWNTs.

Preparation of a high dispersibility graphene oxide (GO) that can be reliably used in biological investigations is reported by Kostas Kostarelos and co-workers on page 433. Exposure of cells and tissue to the graphene oxide indicated a lack of cytotoxic responses in human cell cultures (in vitro) and after injection to living animals (in vivo).

Prompted by the excitement from the description of single layer graphene, increased attention for potential applications in the biomedical field has been recently placed on graphene oxide (GO). Determination of the opportunities and limitations that GO offers in biomedicine are particularly prone to inaccuracies due to wide variability in the preparation methodologies of GO material in different laboratories, that results in significant variation in the purity of the material and the yield of the oxidation reactions, primarily the Hummers method used. Herein, the fabrication of highly pure, colloidally stable, and evenly dispersed GO in physiologically-relevant aqueous buffers in comparison to conventional GO is investigated. The purified GO material is thoroughly characterized by a battery of techniques, and is shown to consist of single layer GO sheets of lateral dimensions below 500 nm. The cytotoxic impact of the GO in vitro and its inflammation profile in vivo is investigated. The purified GO prepared and characterized here does not induce significant cytotoxic responses in vitro, or inflammation and granuloma formation in vivo following intraperitoneal injection. This is one of the initial steps towards determination of the safety risks associated with GO material that may be interacting with living tissue.

Drug release triggered by an external non-invasive stimulus is of great interest for the development of new drug delivery systems. The preparation of an electroresponsive multiwalled carbon nanotube/poly(methylacrylic acid) (MWNT/PMAA)-based hybrid material is reported. The hydrogel hybrids achieve a controlled drug release upon the ON/OFF application of an electric field, giving rise to in vitro and in vivo pulsatile release profiles.