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Improvement of the clinical applicability of tissue-engineered vascular grafts, as new regenerative therapy for children with congenital cardiovascular malformations

Description

Currently available artificial graft prostheses for congenital disorders lack the capacity of growth and often require complex and reconstructive surgical interventions. As a consequence, repetitive and high-risk surgical interventions during childhood are inescapable, associated with increased morbidity and mortality. This not only raises enormous costs for the society, but compromises the quality of life of the young patients. Therefore, manufacturing Living Vascular Grafts is the ultimate goal for both cardiovascular researchers and clinicians. Tissue engineering is an opportunity to create prostheses that are vital, growing, adaptive, and autologous and show optimal functionality. Such in-vitro tissue-engineered vascular grafts have demonstrated functionality and growth as pulmonary replacement in lambs. However, classical tissue engineering using autologous cells, necessitates invasive cell harvesting from the patient, time consuming cell expansion and production of the patient-specific graft. As the living cellular component of the grafts inherently limits clinical applicability, an accelular equivalent with corresponding strength, growth, and regenerative capacity, would provide an attractive alternative for the living tissue-engineered vascular grafts. Therefore, my goal is to improve the clinical applicability of the tissue-engineered pulmonary grafts by decellularizing them, therewith creating novel off-the-shelf constructs for children with congenital cardiovascular malformations. The in-vivo recellularization capacity of these accelular tissue-engineered pulmonary grafts will be evaluated in a pre-clinical animal model to demonstrate their potential to grow with the recipient. These innovative alterations to create unlimited off-the-shelf grafts will speed up the clinical translation of this novel concept. It will inherently favor the wellbeing of patients by reducing waiting time and avoiding reoperations, in addition to a reduction in health costs.

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