• Repairing broken hearts: Living, tissue-engineered blood vessels for the treatment of congenital heart defects

    New NCRC-funded research from the Tissue Engineering Research Group at UCD has led to the development of a next generation living heart implant with the potential to be used to treat children with congenital heart defects.

    About 1% of children born are diagnosed with a structural defect of the heart. The surgical treatment for these defects often requires the implantation of a vascular graft (a structure connecting two blood vessels together) which helps blood to flow around the defect as part of a reconstructive surgery – essentially ‘re-plumbing the heart’. A significant limitation in the field is the inability of current synthetic blood vessel materials to grow and remodel as the patient gets older, meaning that children with these structural heart defects will outgrow their synthetic grafts and require re-operations to implant larger grafts.

    Tissue engineering involves the use of cells and biodegradable materials to grow living implants that can replace lost or defective tissues or organs. A rapidly maturing field, tissue engineering is on the cusp of delivering impactful new medical devices which, for paediatric patients in particular, offer the prospect of implants that are uniquely suited to their needs. To date, tissue-engineered vascular grafts have shown some limitations, including the absence of ‘elastic fibres’, which help to protect vessels in the body against over-expansion. Such expansion and stretching of the graft wall could ultimately result in vessel weakness and possible vascular complications later in life.

    In a newly published study, led by Dr Ian Woods and Dr Tom Flanagan, the Tissue Engineering Research Group has produced a novel vascular graft, constructed primarily from materials and cells isolated from the umbilical cord of the infant – removing the potential for graft rejection, and providing the child with a living graft capable of growth. In addition, the graft has both the strength, layered structure and elastic components of the body’s blood vessels, overcoming many of the limitations of earlier grafts.

    The production of the graft involves taking a blood sample, extracting a blood protein (fibrinogen) that is involved in wound healing, and using that protein together with a biodegradable polymer to manufacture a temporary tubular structure, upon which an infant’s cells (removed from the umbilical cord) can be seeded. The base material is designed to mimic the environment that cells experience within a human blood vessel – by weaving smaller-than-microscopic fibres (called nanofibres) out of the fibrinogen blood protein. A mesh produced from these fibres forms a natural support structure that acts as a scaffold for the cells to lay down the building blocks of the replacement tissue. But, as Dr Wood highlights, the method of vessel production, as well as the materials used, has introduced considerable advantages over previous grafts and fabrication methods:

    “Electrospun materials have such small fibres – they can help to direct how cells behave – but the small gaps between fibres make it very difficult for cells to squeeze between them and move in from the outer surface. So we took a very different approach, inspired by the normal layered structure of the cylindrical blood vessel wall: we grew cells on a ‘sheet’ of electrospun material, before rolling the sheet and cells together, almost like rolling a cigarette paper, into its final form for further maturation as a blood vessel. What we end up with is a structure that becomes knitted together by the cells.”

    Figure 1: Process for developing the vascular graft

    Dr Woods and the team have demonstrated that, over time, this technique can be used to produce living grafts that mimic the structure of a human blood vessel.

    The Tissue Engineering Research Group at UCD has an established research programme focussed on the development of next-generation cardiovascular devices for children, including novel vascular grafts, heart valves and stents. The group will now be seeking further funding to test their vascular grafts in a suitable animal model together with their clinical collaborators in paediatric cardiac surgery.

    Dr. Flanagan, who leads the Tissue Engineering Research Group, is looking forward to the next challenge: “We are delighted that the efforts of the team, and particularly Ian’s hard work and dedication, have come to fruition with this device; the next step will be to determine initial safety and efficacy of these grafts in an animal model, with a view to one day being able to accelerate recovery in children with complex cardiovascular anomalies.”

    This research is published in the international peer-reviewed journal “Journal of Tissue Engineering & Regenerative Medicine”, and was funded by the National Children’s Research Centre, Crumlin, and the Children’s Medical and Research Foundation, Crumlin.

    The complete publication can be found through the following link:

    Woods I, Black A, Molloy EJ, Jockenhoevel S, Flanagan TC. Fabrication of Blood-Derived Elastogenic Vascular Grafts Using Electrospun Fibrinogen and Polycaprolactone Composite Scaffolds for Pediatric Applications. J Tissue Eng Regen Med. 2020 Jul 12 [Epub ahead of print] (Pubmed)