"Oesophageal cancer is the sixth most fatal cancer in worldwide and often requires surgical removal alongside chemo- or radiotherapy. The surgical treatment options available are highly invasive and have a large impact on a patient's quality of life. Oesophageal tissue is complex and has poor regenerative capacity meaning further surgical repair is usually required after oesophagectomy, often using stomach or colon to replace lost oesophageal tissue (1). Common surgical repair techniques have high rates of mortality and are associated with many complications (2).
We are developing a biomaterial scaffold to be used as part of a regenerative medicine approach to the repair of oesophageal tissue. This has the potential to improve many patient outcomes by removing the need for a further surgical procedure to obtain donor tissue, which is often not able to restore full function to the area.
Electrospinning is often used to produce biomaterial scaffolds for regenerative medicine as the resulting nanofibres are similar in structure to the extracellular matrix. Aligned fibres in particular have been shown to increase migration into a wound site from surrounding tissue (3). While there are many benefits to using electrospun synthetic polymers as a biomaterial scaffolds, they usually must undergo significant post-production processing to maximise their suitability.
We have used electrospinning to produce sheets of aligned polycaprolactone (PCL) nanofibres with a fibre diameter as low as 100 nm. This fibre diameter is similar to that being used for successful tissue engineering by several groups, and within the range of the oesophageal ECM fibre diameter (28-165nm). PCL was chosen for this study because it has shown promise as an implantable biomaterial for several regenerative medicine applications, including in the form of electrospun nanofibres. PCL nanofibres are biocompatible and biodegradable, but not very bioactive or hydrophilic.
We are investigating the effect of several postproduction processes on the activity of oesophageal fibroblasts when seeded onto the electrospun PCL scaffold. We have functionalised PCL nanofibres with fibronectin via hydrolysis, which also increases the wettability of the scaffold (4). We have developed a method to imprint micro scale (25 um) grooves onto the surface of a sheet of PCL nanofibres allowing us to investigate how cells respond to different scales of topographical alignment.
It is also important when developing a biomaterial scaffold to be aware of the mechanical forces that it will experience once implanted into the relevant in vivo environment. We have investigated the effect of four different sterilisation and disinfection methods on mechanical properties of PCL nanofibres, to determine whether they can be used to sterilise the scaffolds without degrading it to the point of no longer being suitable for in vivo implantation.
1 Badylak, S.F. et al., Tissue Eng. Part A. 17, 1643-1650 (2011)
2 Poghosyan, T. et al., J Pediatr. Gastroenterol. Nutr. 52 Suppl 1, (2011)
3 Ottosson, M. et al., PLoS One. 12, (2017)
4 Liverani, L. et al., Front Bioeng Biotechnol. 7, 68 (2019)"