Creating a simplified and standardised bioreactor system for tissue-engineered vascular graft culturing and characterisation

Creating a simplified and standardised bioreactor system for tissue-engineered vascular graft culturing and characterisation

Visser, Dmitri (TU Delft Mechanical, Maritime and Materials Engineering; TU Delft Biomechanical Engineering; TU Delft Biomaterials & Tissue Biomechanics)

Hinderer, Svenja (mentor)
Fratila-Apachitei, Lidy (mentor)
Zadpoor, Amir (graduation committee)
Kenjeres, Sasa (graduation committee)

Delft University of Technology

Biomedical Engineering

2018-12-05

With the recent developments in tissue-engineered organ substitutes, there has been an increasing demand for novel culturing techniques to create biological substitutes in vitro, as well as reliable and efficient test methods that can assess their biocompatibility and mechanical performance. In the past two decades, perfusion bioreactors have proved to be important tools in the creation, control, and evaluation of cell cultures and engineered tissues under precisely controlled in vitro conditions that simulate the physiological environment. Due to the demanding requirements for blood vessel substitutes, they have been extensively deployed in the culture and conditioning experiments of novel tissue-engineered vascular grafts (TEVGs) and have been often used to study haemodynamic mechanic stimuli, including the cyclic vessel expansion and wall shear stress. However, a key limitation of the currently available TEVG perfusion bioreactors is their often complex design and operation and the lack of standardisation of the mechanical characterisation.
In this study, the goal was to design, characterise, and construct a TEVG perfusion bioreactor that is foremost simpler to operate and extends the capabilities of particular currently available set-ups. A modular bioreactor design is presented that allows for the toolless mounting of the graft with a diameter up to 6 mm and features completely separated circuits for the intra- and extraluminal side of the scaffold wall. The culture chamber encloses a removable graft frame, mainly machined out of polyether ether ketone (PEEK). In silico simulations have been used to assess local fluid dynamics within the scaffold, to predict the reliability of the simulated culture conditions. The presented design allows the exertion of a broad range of physiologically relevant shear stresses on cultured TEVGs, including arterial shear stresses. A test for the in vitro cytotoxicity showed that the medium extracts of the constructed graft frame did not show any cytotoxic potential. Finally, an assessment method for the estimation of the radial compliance is proposed, which aims to adhere to the relevant international standards on the mechanical characterisation of vascular substitutes.

bioreactor
cardiovascular disease
tissue engineering
Blood vessels

http://resolver.tudelft.nl/uuid:719c107b-67a2-497d-991a-a70b0cb992aa

2020-11-23

Student theses

master thesis

© 2018 Dmitri Visser