A 2012 research paper 1 has opened a promising new avenue in tissue engineering, one that starts to address the problem of spatial discrimination within tissue scaffolds. Nanofibers need to be continuous in order to promote cellular attachments, but they also need to be layered and arranged in 3 Dimensional forms which will entrain the correct growth of complicated tissues. An answer may emerge from an exciting technique where c.10µm diameter microcapsule nests of 100-200nm diameter nanofibers may be laid to form bespoke, finely shaped tissue scaffolds of biodegradable polylactic acid (PLA).
This technique diverges from the usual electrospraying process by inducing phase separation in the fluid. Typically, charged fluid is drawn from the nozzle as a narrow jet, which splits into large droplets, which in turn split repeatedly because of their mutual electrostatic repulsion. Since these droplets are highly exposed to air, they will rapidly dry, leaving any remaining solute as a solid or gel nanoparticle.
In the case of the nanofibrous microcapsules, the fluid that flows from the nozzle is made up of PLA, chloroform and ethanol. Chloroform is PLA's preferred solvent, whilst ethanol is poorly miscible with the chloroform. If water is available to the ethanol, it will preferentially absorb it, becoming immiscible with the chloroform. This way, the PLA molecules will be forced into the chloroform.
On being electrosprayed into droplets in sufficiently humid conditions, the ethanol takes on water, causing a phase separation where pockets of ethanol and water grow and separate from the PLA-chloroform solution within the droplet. Since the PLA and chloroform carry much of the original charge from the nozzle, this chloroform material has greater charge density, such that it is forced to the surface of the expanding droplet due to electrostatic repulsion. Exposed in this way, much of the volatile chloroform evaporates as the particle falls, leaving PLA nanofibers on the surface.
If these new microcapsules are deposited onto recently sprayed microcapsules that are yet to completely dry, these wet nests will fuse and stack, although they otherwise retain their structural integrity. Since the nanofibrous capsules can be laid wet enough to adhere to one another, it has been possible to vary the modular structures they produce, from sheets, to cups, to columns with the help of electrostatic lenses that are readily able to focus output into areas with diameters as low as 200µm.
As a technique with the potential to advance tissue engineering by closely arranging discrete, nanofibrous building blocks with air, water, and cell permeability, these nanofibrous microcapsules were tested as scaffolds for the human HepG2 cell line. The results were encouraging, with excellent cellular proliferation through the scaffold and an above average metabolic rate for the cells. However, this leaves a great deal of unknowns, including the longer-term cellular survival in a graft, and the impact of the microcapsulesÕ atypical scaffold shapes on cellular behaviour and development. Addressing these questions will at the very least require thorough long term studies which will likely identify problems in the technique. Further development will require the controlled adjustment of multiple process parameters such, flow rate, polymer type, humidity, solvent miscibility, collection distance, Spraybase systems are designed to help researchers make these investigations with far greater ease.
 doi: 10.1007/s10544-011-9583-x