July 2012

UCD Investigator Awarded Funding for Project To Improve Surgical Treatment of Congenital Heart Defects

Tue, 31 July 12 09:00

Tom FlanaganThe project is entitled “Autologous, elastogenic tissue-engineered vascular conduits for repair of congenital heart defects”. This project grant will provide funding to train a PhD student in a highly multidisciplinary study, which aims to produce a novel, autologous elastogenic vascular graft that can be constructed entirely from materials isolated from the infant patient. The premise of this study is that autologous, or ‘self-made’, materials will remove the potential for graft rejection, and provide the infant patient with a living, elastic graft that can grow together with their surrounding body tissues, thereby eliminating the need for successive re-operations.

Dr. Flanagan, based at UCD School of Medicine and Medical Science,  has worked closely with Prof. Jockenhoevel over the last number of years developing techniques to generate living vascular grafts and heart valve prostheses based on a fibrin gel scaffold material. Fibrin can be isolated from a sample of patients’ blood, and used as a material on which to grow cells, which then transform the fibrin into a tissue-like structure.

The group has been working extensively on identifying suitable cues to encourage the appropriate type of tissue formation, and these include mechanical cues (e.g. bioreactor conditioning) and biochemical cues (e.g. growth factor supplementation). The current 4-year translational study will employ novel techniques to generate more stable, long-lasting vascular graft materials using specialised equipment, defined chemical supplementation, together with the patient’s own cells.

Project Summary:

Congenital cardiovascular defects are present in about 1% of all live births. Children born with a single pumping chamber, for example, are considered a mortality risk. The treatment of choice for such defects is staged surgical reconstruction, with the final stage involving re-plumbing of the heart with a vascular graft conduit.

A significant limitation in this field is the inability of current graft materials to grow and remodel as the patient grows. Tissue engineering has emerged as an exciting alternative for the production of living vascular conduits with the potential for growth and remodelling within the patient.

A significant limitation with current tissue-engineered conduits is stretching of the wall after implantation with a consequent risk of graft rupture. It is thought that the absence of elastic fibres, which protect vessels against over-expansion, may ultimately be responsible for this expansion. This study aims to produce a novel vascular conduit that can be constructed entirely from materials isolated from the infant. A tubular scaffold material will be designed and tailored specifically to encourage formation of elastic walls by living cells, while biochemical supplementation and mechanical conditioning will be optimised to promote the development of mechanically stable tissue.

It is anticipated that the results of this study will form a substantial basis for the clinical application of patient-grown tissue-engineered vascular conduits in the repair of congenital cardiovascular defects.

The project is entitled “Autologous, elastogenic tissue-engineered vascular conduits for repair of congenital heart defects”. This project grant will provide funding to train a PhD student in a highly multidisciplinary study, which aims to produce a novel, autologous elastogenic vascular graft that can be constructed entirely from materials isolated from the infant patient. The premise of this study is that autologous, or ‘self-made’, materials will remove the potential for graft rejection, and provide the infant patient with a living, elastic graft that can grow together with their surrounding body tissues, thereby eliminating the need for successive re-operations.

Dr. Flanagan, based at UCD School of Medicine and Medical Science,  has worked closely with Prof. Jockenhoevel over the last number of years developing techniques to generate living vascular grafts and heart valve prostheses based on a fibrin gel scaffold material. Fibrin can be isolated from a sample of patients’ blood, and used as a material on which to grow cells, which then transform the fibrin into a tissue-like structure.

The group has been working extensively on identifying suitable cues to encourage the appropriate type of tissue formation, and these include mechanical cues (e.g. bioreactor conditioning) and biochemical cues (e.g. growth factor supplementation). The current 4-year translational study will employ novel techniques to generate more stable, long-lasting vascular graft materials using specialised equipment, defined chemical supplementation, together with the patient’s own cells.