iTRACH · Development & characterisation of a pre-vascularised tubular scaffold for tracheal regeneration that supports the formation of an iPSC-derived epithelium

Tracheal damage is often life-threatening, and its incidence has increased due to invasive mechanical intubation of COVID-19 patients. Short defects undergo a surgical procedure (anastomosis), but this is not feasible for extensive defects. While bioengineered approaches for such defects have been investigated, there has been little translation into the clinic as implants weaken over time and fail to support the formation of neotracheal tissues. I aim to solve this problem by developing and characterising 3D printed tubular scaffolds for use as medical devices for tracheal restoration via a Global Fellowship involving Royal College of Surgeons in Ireland and Boston University, followed by a non-academic placement in CellInk. Scaffolds will be designed to mimic tracheal biomechanics and will be extensively characterised. Induced pluripotent stem cells (iPSCs) will be used to develop a pre-vascularised mature respiratory epithelium on disc scaffolds in combination with endothelial progenitors and human mesenchymal stem cells (hMSCs). The tri-culture will then be moved into the tubular design and the pre-vascularised mucosal substitute will be grown and assessed in vitro as an approach for ex vivo seeding of tracheal grafts prior to implantation. The ability of the tubular scaffold to support the growth of cartilage tissues will be assessed using a combination of bioprinting and differentiation of hMSCs. iTRACH will provide me with crucial training in advanced research skills (iPSCs, stem cell biology, biomaterials & 3D printing) and transferrable skills (Intellectual Property, Project Management, Entrepreneurship, Professional Enhancement and Science Communication). This fellowship will provide me with the required technical and complementary skills to enhance my employability and to allow me to transition into a research position in a leading biomedical company, while also allowing for the possibility of me staying in an academic role with links to industry.