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MANUFACTURING

Electrospinning nanofibres

Expertise in wafer scale micro-fabrication of electrospray sources, which were originally configured as low profile satellite thrusters, is being used to make electrospinning sources that will provide revolutionary nanofibre-based structures and coatings for the medical device industry. Materials made of nanofibres have special properties that can be harnessed for novel applications in healthcare and research is being conducted in a variety of fields by scientists at the Micro and Nanotechnology Centre (MNTC) at the United Kingdom's Science and Technology Facilities Council. The main characteristics of nanofibre materials are large surface area and porosity. This proves particularly useful for wound dressings where the small pores allow the dressing to breathe whilst keeping microorganisms away from the wound. Another advantage of nanofibre meshes is that they mimic the extracellular matrix by providing structural support for cells and act as a store for growth factors, growth inhibitors and antimicrobial agents. This provides a good base for cells to attach, differentiate and grow. Cells can grow on the surface of the fibre mat or migrate into the spaces between fibres. For orthopaedics, the nanofibre materials could be used as biomolecule carriers for nano composite cements or to form a specialised stage release biomimetic coating on metal or plastic implants to control the regenerative process of new supportive tissues that surround the implant. These types of coatings are expected to lead to "once only fit" cementless implant procedures for large and small orthopaedic implants. A "living interface," which would evolve between the bone tissue and the implant, would reduce the chance of infections and therefore lead to a reduced number of revisions. This is critical to reducing the burden on healthcare services whilst enhancing quality of life. Combined with their inherent structural strength, the mats can be used in many aspects of regenerative medicine, including tissue engineering, cell therapy and drug delivery.

The electrospinning process

Figure 1: Nonwoven polymer nanofibre mat produced by electrospinning. (click image to enlarge)

Electrospinning is probably the most versatile and economic method of producing polymer nanofibres (Figure 1). Almost any polymer that can be dissolved can be processed in this way. The most basic components required for electrospinning are a pump, a syringe, a syringe needle, a high voltage supply (several kV), a controlled processing environment and a collector for the fibres.

To electrospin nanofibres, a chosen polymer is mixed with a suitable solvent to produce an electrospinning solution. The system is primed and a droplet is formed at the syringe tip. A high voltage is applied between the needle and the collector, which creates a high electric field. The electrostatic forces cause the droplet to elongate. When the electrostatic forces are sufficiently large, surface tension is overcome and a thin jet appears from the apex of the elongated droplet. The jet consists of solvent, long polymer molecules and stored charge or ions. As the electrostatically charged jet is pulled towards the collector, the volatile solvent evaporates from the jet. This causes the polymer molecules to move closer together with an increased chance of the molecules entangling with each other. The shrinkage increases the electrostatic charge density and repulsive forces increase within the fibre. This force causes the fibre to extend along its axis and the polymer molecules to slide over each other. This continues until there is no more solvent in the fibre and a dry fibre lands on the collector: a nanofibre.

Fibres can be customised not only through the choice of polymers, but also by incorporating different agents, for example antibacterial, antibiotic or therapeutic agents. These may be added to the polymer solution, sprayed over the fibre mesh or encapsulated in special, concentric fibres.

Areas of research

Figure 2: Part of an array of 20000 of silicon nozzles for electrospray and electrospinning applications. (click image to enlarge)

The electrospinning team at the MNTC is developing the technology to produce these fibres. The team is particularly interested in providing the systems to encapsulate agents for tissue repair and cell growth, and as a result is developing a selection of special electrospinning sources. These are used to produce multiwalled, concentric fibres that can contain different polymers and agents in each section, targeting for example different stages in a healing process. For an orthopaedic coating, the researchers are developing a core multishell electro-spinning source, where the core of this complex fibre will contain bone growth factor, the adjacent shell or coating would contain vascular growth factor and the outer shell would contain an antibacterial agent. The thickness and type of biopolymer chosen would determine the degradation profile of the fibre, which in turn would control the release kinetics of the bioactive agents. Excellent process control is required to maintain consistency of fibre cross-section and the distribution of functional agents within the fibre. This will allow the antibacterial agent to denature bacteria lying in the vicinity of the bone tissue interface. This promotes vascularisation to provide the necessary blood vessels to support the regenerative process and finally release the bone growth factor for cellular production of bone matrix.

Two conventional colbalt chrome implants, one with a nanofibre coating the other uncoated.

One significant problem the electrospinning industry faces is the quantity of fibres produced. The standard, single needle method discussed above can only produce quantities in the range of mg/h. Over- coming this limitation is another focus of current activity. Work is underway on the development of deployable electrospinning modules that enable a massive increase in production rate compared with single nozzle electrospinning sources (Figure 2). Initial prototypes have produced nanofibres with a significant increase in production rate. The design is being enhanced for low cost manufacture of the source. This will allow large areas or volumes of functionalised fibres to be produced for a wide range of applications, especially in the healthcare, energy and environment sectors.

The team is engaged on research programmes with different partners to develop cell-based therapies for eye disease, spinal cord repair, orthopaedic implants and enhancement of the immune system. In 2008, its work on surface engineering to improve orthopaedic implants won the Medical Futures Translational Research Innovation Award in Orthopaedics (www.medicalfutures.co.uk). The award was granted for the intelligent nanofibre coating described above. Currently, the process of bonding bone to an implant requires a cement. However, after several years of use, infections may cause cemented implants to loosen, which then requires corrective surgery. Conversely, nanofibre coatings on the implant could provide a natural biomimetic structure for cells to attach and grow into, eliminating the need for the cement (Figure 3). The researchers are commercialising the electrospinning technology with the aim of making electrospinning equipment available to the market. The team is always interested in new collaborations and in exploring ideas for new materials.

Dr Robert Stevens, Principal Scientist, Science and Technology Facilities Council, Micro and Nanotechnology Centre, Rutherford Appleton Laboratory, Harwell Science and Innovation Campus, Didcot OX11 0QX, UK, tel. +44 1235 445 000, e-mail: bob.stevens@stfc.ac.uk www.stfc.ac.uk