Electrospun silicone microthreads for regenerative medicine
In a collaborative research project between the Departments of Biochemistry and Molecular Biology, and Mechanical Engineering at University College London (UCL), UK, scientists have for the first time demonstrated the feasibility of using electrospinning technology to produce polymeric threads that contain viable brain cells. These threads are of the same order of magnitude as the cells they encase.
Funded by the Royal Society, UK, the project was inspired by a BBC programme that showed a surgeon removing a tumour from a human brain while the patient was still conscious. The surgeon was able to monitor how memory and speech were affected by brain tissue damage and stimulation occurring during the procedure.
The ability to electrospin biologically active threads and scaffolds of living organisms will be tremendously useful for the development of a whole host of novel bioengineering and medical applications,' says Dr Suwan Jayasinghe, Project Leader at UCL.
Round and around
Electrospinning is a jet-based technology that is driven solely by electric fields created by an applied potential difference between the jetting needle and a ground electrode.
Traditionally, it has been used to make nanoscale fibres and scaffolds, but Jayasinghe's group has spearheaded the incorporation of living cells into the constructs. This was previously difficult as there were several constraints that had to be met to maintain of the physiological properties of the cells. One of the main limitations was the difficulty in electrospraying in a stable jet mode, principally because the viability of cells requires a high concentration of ions in the medium in which they are electrosprayed.
Solving the problem
Jayasinghe's team has recently discovered that the use of co-axial bio-electrospraying resolves this jet instability. In this process, a needle within a needle arrangement is used where a concentrated viable biosuspension flows through the inner needle and a medical-grade poly-dimethylsiloxane (PDMS) medium, with high viscosity and low electrical conductivity, flows through the outer needle.
By applying an electrical field of approximately 9.5kV, a droplet of the viscous polymer is stretched into a superfine thread no wider than the cells themselves using the polymer's inherent electrostatic repulsion. The silicone material forms a fibre around the cells. Cells encapsulated in the polymeric threads were harvested and cultured to assess viability. The cells were found to be healthy and showed no evidence of having incurred any damage during the bionanofabrication process.
Dr Andrea Townsend-Nicholson, Co-project Leader says, ‘Our investigation has shown that it is possible to directly electrospin living organisms under stable conditions at a level of resolution that is constrained only by the size of the cells being electrospun.
Examining the thread
Microscopic analysis reveals that the diameter of the threads is dependent on the flow rate through the inner and outer needles at any given voltage. For any flow rate combination, the threading process relaxes if the applied voltage is too low. Conversely, if the voltage is too high, the composite thread acquires an eccentricity that forms a whipping thread, which generates secondary fibres at multiple points along the primary strand.
Optimising the process
So far, the electrospun cells have survived hostile electric fields of up to 2kVmm-1 at a maximum drawing current of 4mA. One of the areas awaiting study, is how the process will affect the biological properties of the cells in the long term. Jayasinghe says, ‘We intend to develop this technology further to achieve deposition of a controlled number of cells within residue threads and to explore how the technology can be applied to fundamental questions in cellular and developmental biology.
He adds, ‘Although we have used poly-dimethylsiloxane liquid in our experiments, its replacement with different biopolymers is possible, allowing modulation of the structural integrity and the half-life of the electrospun threads. [These] would be spun directly onto a wound to assist in rapid healing.
Dr Suwan Jayasinghe, tel +44 (0)207 679 2690, email: firstname.lastname@example.org.