In a spin: The maturing technology of Nanofibres

From biotechnology to thermoplastics and back again – applications for nanofibres seems endless while the electrospinning process has made the tricky move from lab curiosity to commercially viable manufacturing process Initial applications for electrospun nanofibres in the medical field include 3D scaffolds, which provide an ideal substrate for the growth of human cells resulting in major advantages over cells grown in a 2D network, as they closely mimic natural tissues and organs. Cells grown as 2D networks e.g. like the ones grown flat on petri dishes spread on hard plastic surfaces and form unnatural cell attachments, whilst 3D network provides a highly porous and flexible architecture where the cells penetrate the loose scaffold, attach and proliferate to establish clusters. The micro-cellular environment allows exchange of nutrients and expressed proteins. These structures therefore have greater physiological relevance. However in order to take full advantage of the potential of 3D scaffolds by the pharmaceutical industry, the process requires to be compatible with automated testing and imaging systems. The Electrospinning Company solved this problem with their new Mimetix scaffold, which is laser welded into the base of a 96 well plate providing a flat base for imaging and excellent well to well uniformity. The Mimetix plates are sterilised with Gamma radiation and ready for use. Key to the success of this approach is consistent manufacture and quality assurance leading to reproducible performance suitable for drug screening. Spinning nanofibres is not only the prerogative of clever scientists, but is a process found in nature and used by insects such as spiders, bees and caterpillars, as part of their ordinary lives to create a local environment within which they might catch prey or simply grow and reproduce. Oxford Biomaterials is a company which has been developing novel product forms based on silk nanofibres since 2001 and several different companies have been “spun out” to address different market needs. The focus has been on the development and modification of their spider silk-like fibres and scaffolds for the medical device industry. This has resulted in the development of an entirely novel range of absorbable medical devices based on the proprietary Spidrex technology platform. Oxford Biomaterials have spun out two further companies, Orthox (knee meniscal implants) and Neurotex (peripheral nerve guide). Silk is also the nanofibre of choice for studies at Nottingham Trent University. Composites of silica with silk and silk fusion proteins are being studied and although these well organised structures are not fully understood, work is focussed on the synthesis of different forms of silica and their use in a range of composites formed from silk and silk proteins. Experiments have measured the effect of the composites on the up regulation of biochemical markers associated with bone regeneration. The use of the silica materials as effective tissue culture surfaces and the effect of silica associated with alginate beads on the viability of encapsulated mesenchymal stem cells are also being studied. It is interesting to note that although scaffolds for supporting cell growth have been of much interest for many years in the context of regenerative medicine, there have been concerns about the potential for poor cell infiltration throughout the entire depth of the scaffolds. Such problems have limited the use of scaffolds as tissue engineering biomaterials in regenerative medicine. At UCL, the ability to electrospin cells directly with both a biopolymer and other advanced materials for simultaneously forming a 3D living system that imitates native tissues has been demonstrated. Tests are ongoing with this approach. Creating composite structures using nanofibres can be considered in two different ways. Firstly, nanofibres can be incorporated in, for example, a thermoplastic matrix to enhance strength, stiffness, wear resistance and a reduced risk of crack propagation in relatively weak materials. Secondly, a strength yielding fibre can be co-spun using an electrospinning process such that alignment of the nanotubes in the fibre is achieved, leading to enhanced performance of the fibre combination. A start-up company called Spi3Dr Ltd is developing a process to produce 3D printed composites containing an appropriate nanofibre reinforcing polymer. While the industrial 3D printer is capable of producing highly complex structures based on thermoplastics or thermosets, at the low cost end of 3D printing equipment, only thermoplastics can be used. This means that limited performance can be achieved from products produced in this way although at a significantly lower capital and operating cost than with industrial scale printers. Incorporation of nanofibres at the 3D printer print head such that they are incorporated into the polymer as the polymer melts provides an attractive proposition with the ability to switch the nanofibres on and off leading to the potential for patterning at differing nanofibre densities and fibre types. Work continues on this approach with a method of electrospinning carbon nanotubes (CNTs) into a polymer delivered via a 3D printer already demonstrated. This could be an interesting approach to creating some very hard to manufacture shapes and constructions. Thomas Swan & Co. produces high quality single walled CNTs and the company is interested in the inclusion of these materials in advanced composites. CNTs have outstanding electrical and mechanical properties especially when aligned and this makes them ideal for use in advanced composites, but they are notoriously difficult to manipulate especially into the large arrays required of such structures. Using electrospinning with the CNTs co-spun with a carrier polymer, a fully scalable process has been developed in association with the University of Surrey to produce large area sheets of aligned CNT based composites which have resulted in a significant increase in both strength and ductility and a four-fold increase in Young’s Modulus. Copolyimide nanofibres based on BPDA/PDA/ODA have been produced at Queen Mary College, University of London by electrospinning and imidisation from its precursor polyamic acid nanofibres. Mechanical testing is ongoing and the materials produced by this process are under consideration for use in body armour where the potentially highly aligned nanofibres will provide the reinforcement properties being sought for this application. Novel composite nanofibres have also been produced at University of Manchester. In this case, the nanofibres are co-electrospun with an outer sheath covering a central core. While the shell material can be a conventional electrospun polymer, such as PCL, the core may be a material such as PEO, olive oil, mineral oil or sugar water solution and may be removed after co-electrospinning leaving a novel hollow fibre construction. Applications for such constructions are being developed given the range of material combinations that might be possible. Revolution Fibres were set up in New Zealand in 2009 to produce nanofibres with an initial product focus on filters for home filtration units. Production has been scaled up to 800 g/hour of nanofibre at present using a fully enclosed and controlled unit capable of producing mat of 2m width. Various products have been developed including interlaminar reinforcement for carbon fibre composites such as fishing rods and a soluble marine collagen skincare product. Revolution Fibres are currently looking for partners to extend their product and application ranges and could potentially manufacture in the UK if such a partnership justified producing the product locally. Finally, combining electrospinning with existing commercial processes is how this technology will provide significant benefit and value to the producer and to the user. One very interesting approach is to combine offset lithographic printing with laying down electrospun nanofibre mats potentially in a pattern. The iSMART facility at Nottingham Trent University is where this all began. A grant from the European Regional Development Fund supports free access to eligible SMEs to the electrospinning expertise, two pilot scale synthesis systems and specialised nanofibre characterisation equipment, including a Phenom ProX SEM with EDS and Fibermetric analysis. Collaboration with a company called Nano Products Ltd has led to the capability to produce a range of printed products overlaid in a controlled manner with electrospun nanofibre mats. Potential applications under consideration/development based on this structure include disposable diagnostic sensors, sterilisation units for water, flexible dye-sensitive solar cells, affinity membranes and components for regenerative medicine. The electrospinning process, although still being optimised for many different applications is no longer a university laboratory curiosity. Commercially produced nanofibres and mats are now available and composite structures addressing real market need are being produced. This synthetic approach complements the work done to produce natural nanofibres such as silk which given its inherent biocompatibity is likely to find lots of exciting applications in the medical world. Authors Dr Barry Park, Theme Manager, NanoKTN, Professor Bob Stevens, Professor of Smart Materials and Devices, iSMART Project Director, School of Science and Technology, Clifton Campus, Nottingham Trent University and Dr Gabriela Juárez Martínez, Theme Manager, NanoKTN