Bio-fabricating constructs suitable for pulmonary valve replacement therapy in paediatric patients with congenital heart defect

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


Congenital heart disease (CHD) is the highest recurring form of heart defects in paediatric patients with a frequency of 75 in every 1,000 live births. Modern advances led to a higher survival rate of children born with CHD into adulthood. However, adult CHD patients are not cured from the disease, they are only temporarily treated. This study attempts to fabricate a biocompatible amnion-based scaffold that can grow and regenerate, acting as a suitable construct for pulmonary valve replacements in children with CHD. To create the “off the shelf” amnion-based scaffold, the amnion was enzymatically decellularized and preserved by freeze-drying. The biocompatibility and biomechanical properties of different number of layers were examined to identify the optimal number of layers for different cardiac positions. Results showed that 4-8 layers are optimal. The amnion-based scaffold provided support for seeded mesenchymal stem cells. The higher number of amnion layers allowed more cells to attach and thrive onto the scaffold. In an attempt to enhance layer-layer adherence of the amnion scaffold, the cytotoxicity of four potential glues were tested. Liquiband® Optima, TISSEEL, and ARTISS were cytotoxic while porcine skin-derived gelatine enhanced cell growth on the amnion scaffold. The bio-fabrication protocol was upgraded to a GMP-grade xeno-free protocol. Recombinant xeno-free decellularization enzymes were used and human platelet lysate was used as a gelatin substitute. The GMP-grade protocol was optimal. The amnion-based scaffold was tested in vivo demonstrating its initial success as a potential cardiovascular scaffold for children with CHD. Following the successful fabrication of the amnion-based scaffold, pig aortic and pulmonary valve leaflets were examined as potential cardiovascular scaffolds. The engineered pig leaflet-based scaffolds were biocompatible and their biomechanical properties were suitable for cardiac positions. However, further investigation and optimization is necessary before moving forward to in vivo testing in an animal model.
Date of Award22 Mar 2022
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorMohamed Ghorbel (Supervisor) & Massimo Caputo (Supervisor)

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