There are a wide range of cases where the human body is unable to heal naturally as a result of serious trauma or disease. Cases such as second- and third-degree burns, damaged blood vessels and large bone defects may require grafting procedures to complement and facilitate the complete healing of the damaged tissue.

Repair of large bone defects, which are unable to heal naturally, are typically achieved by transplanting bone from one part of a patient’s body, such as the pelvis, to the defect site to promote regeneration (termed autografting). Bone obtained from a donor may also be utilised for this procedure (termed allografting). These approaches, however, have significant limitations in terms of tissue availability as well as the introduction of a second surgical site for autograft procedures. Therefore, recently there has been an increase of interest in using artificially fabricated synthetic biomaterials for implant,that mimic the healing properties of native bone achieved through the auto/allografting procedure. This approach has major advantages over traditional procedures in that only one surgical site is needed (reducing infection risk), in addition to overcoming the issue of limited tissue availability for transplant. There are already a wide range of biomaterials that have been investigated and studied in terms of their ability to promote tissue regeneration, which can be used and modified depending on the application and tissue of interest. In addition to the material, engineers have come to realise that the architecture and mechanical properties of these biomaterials is a critical feature that needs to be optimised to ensure that the material can act as a scaffold for tissue regeneration, mimicking that of the native tissue.

Controlling microstructure of tissue engineering scaffolds

The vast majority of tissue throughout the body, particularly within the musculoskeletal system, is made of a nano/micron sized, fibrous-like extracellular matrix that acts as a template delivering both chemical and physical regenerative cues to resident cells. One aspect of synthetic scaffold fabrication in which many approaches are currently limited is the level of control which is maintained over scaffold architecture at this scale. This often overlooked and integral aspect of scaffold fabrication is crucial to ensure the success of the scaffold in terms of promoting cell infiltration, regeneration and engraftment with the native tissue. While scaffold fabrication techniques such as 3D printing are excellent at controlling architecture on a macro-scale, control of the microstructure is limited. The electrospinning approach is excellent at creating microscopic fibres that mimic the fibrous nature of extracellular matrix. However, this technology is limited due to the random nature in which the fibres are positioned. Melt electrospinning writing (MEW) is a recently developed technology that bridges the gap between 3D printing and electrospinning, having the capability of controlling the spatial organisation of micron diameter fibres in three dimensions. In this approach, a reservoir of material is melted and then slowly passed through a needle (the spinneret), at which an extremely high voltage in the range of kilovolts is applied, resulting in the electrostatic repulsion and stretching of the material into a microscopic fibre. In standard solvent electrospinning, deposition is characterised by a large unstable region and random deposition in the unstable region, with the large distance between the spinneret and collector required to allow for evaporation of the solvent (Fig. 1A).

If, however, the solvent is omitted and the material melted, this large distance to allow solvent evaporation is no longer required, and the collector can be brought up into the domain of the stable region to allow for controlled deposition. In this state, the fibre can then be continuously deposited in a controlled manner to build up a scaffold of the desired architecture (Fig. 1B). We designed and built a custom MEW apparatus that combines electrospinning technology with direct writing, while also omitting solvents to improve biocompatibility. The great level of control that can be achieved during the fabrication of fibrous scaffolds is unique to MEW, and makes it an extremely attractive approach for the fabrication of scaffolds which mimic the fibrous microstructure of many tissues such as bone. The result of this extremely precise level of control can be seen when comparing a solvent electrospun scaffold to a MEW scaffold (Fig. 2). In the latter, complete control over fibre deposition allows for direct control over the scaffold porosity, the size of the fibres and the shape and size of the resulting pores, all features which contribute to regeneration and repair and can be tailored for a given tissue.

Future developments in melt electrospinning writing

Melt electrospinning writing is a technology that is very much still in its infancy, having only been demonstrated for the first time in 2009. However, it can already be seen to have immense potential. The level of control that can be achieved over scaffold microarchitecture not only benefits the creation of more sophisticated and representative scaffold designs for bone tissue engineering, but also opens up a wide range of advanced applications, for example, complex interface tissue engineering. One example of this is the bone ligament interface, characterised by the transition from a regular porous architecture in bone to a highly aligned and fibrous architecture in the ligament, which can potentially be replicated in great detail by the MEW process. Furthermore, these fibrous scaffolds could be further functionalised to act as a drug-delivery systems to further promote healing or prevent infection. The technology also opens up a host of other potential applications, such as the fabrication of biomimetic 3D cell culture systems for the study of cell behaviour in the laboratory. This more realistic environment would offer huge advantages over the limitations of current 2D cell culture systems, which do not replicate the 3D fibrous tissue environment and often lead to inconsistencies between laboratory findings and animal/human trials. In conclusion, while MEW is still a young technology, its potential along with the range of possible future applications are vast. The ease of use of melt electrospinning writing and the level of control over microarchitecture make it highly promising for future commercial applications of this innovative direct writing technology, with great potential in the fields of tissue engineering, regenerative medicine and advanced cell-culture platforms.

Authors: Kian F. Eichholz (1,2,3) and David A. Hoey (1,2,3,4) 1 Department of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick 2 Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin 3 Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin 4 Advanced Materials and Bioengineering Research Centre, Trinity College Dublin & Royal College of Surgeons in Ireland Kian Eichholz won the Best Paper Award, sponsored by Engineers Ireland, at the 2016 Sir Bernard Crossland Symposium. His paper was entitled: 'Design and Manufacture of an Innovative Biofabrication Method for 3D Tissue Engineering Constructs.'