Development of a new microRNA-functionalized composite scaffold as a valve substitute

  • Marco Fagnano

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


Heart valve disease (HVD) is a growing medical issue in western countries. The majority of HVD is of degenerative etiology, the incidence of which increases along with the increase of life expectancy. When the valve function is impaired, the best solution is the implantation of either a biological or a mechanical prosthesis. Current biological prostheses have limited durability, due to degeneration, and calcification risk. The mechanical prostheses bear the risk of thromboembolism or bleeding due to the mandatory anticoagulation therapy.
Tissue engineering research aims to regenerate a native-like valve through a path in which exogenous material and self-generated tissues are progressively integrated. Eventually, the exogenous material will be completely degraded leaving a working valve made of autologous tissues only. The current challenges of this approach are the long-term duration due to leaflet retraction and general degeneration, and the formation of a complete endothelial lining in the shortest possible time.
This project aims to create a microRNA-functionalized scaffold as a potential heart valve substitute through the following steps: i) the selection of a microRNA-vector able to transfect endothelial cells (ECs) and allow the microRNA to regulate cells’ gene expression, without causing toxic or immune reactions; the vector should also withstand the scaffold production process; ii) the investigation of the pro-endothelialization potential of the microRNA hsa-miR-132-3p; iii) the design and fabrication of a scaffold that can locally administer microRNA for a prolonged time, and substitute valve function until the new tissue will be mature enough to take on its duty.
Eventually, this project achieved several objectives. A lipid-based vector that can regulate ECs expression was chosen. A scaffold able to release microRNA for up to 18 days was fabricated. Also, the pro-endothelialization potential of hsa-miR-132-3p on aortic ECs was verified. Finally, aortic ECs seeded on the microRNA-functionalized scaffold were transfected for up to 6 days. The evidence shown in this thesis is a first step towards the development of the new generation of tissue-engineered heart valves that could be successful in clinical practice.
Date of Award21 Jun 2022
Original languageEnglish
Awarding Institution
  • The University of Bristol
SponsorsBritish Heart Foundation
SupervisorPaolo R Madeddu (Supervisor) & Gianni D Angelini (Supervisor)

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