Development of Permanent Artificial Bowel Replacement Substrates

Abstract

Short bowel syndrome (SDS) is a malabsorption disorder caused by loss of function of the small intestine, either by trauma or innately. Current treatment options include parenteral nutrition (PN) or allograft transplants. Long term PN dependence can lead to complications due to line infections and toxicity from the formula itself. A lack of healthy donors results in long waiting lists and high mortality rates. With allograft transplants, long-term graft and patient survival rates are poor (48% and 39% respectively at 5 years); graft loss occurs due to rejection (48%), thrombosis (28%), sepsis (12%); main causes of death are due to bacterial infection (94%) and rejection. Costs associated with PN annually per patient approximate to GBP40,000, whereas one allograft procedure costs approximately GBP80,000; not including intervention due to complications. Interest in developing an off-the-shelf bioengineered alternative have been expressed. Autologous transplants could be a more beneficial route to improving survival rates, enabling the transplant of patients healthy cells back to them. We describe here the development of a synthetic poly(ethylene terephthalate) scaffold using electrospinning, which showed excellent physical and chemical characteristics; high surface area:volume ratio, high mechanical strength, high porosity, and the ability to be chemically/physically functionalised without losing integrity in structure and physical properties. The cost of electrospinning is far lower in comparison to the current available treatment options, potentially providing a stable, off-the-shelf, ready-to-culture product as the need arises for applications in tissue engineered small intestine (TESI), or 3D models for small bowel research.